Statin use is associated with lower risk of atrial fibrillation in women with coronary disease: the HERS trial.

OBJECTIVE: To determine the efficacy of statin treatment in atrial fibrillation (AF) prevention in women. DESIGN: Cohort study using data obtained in the Heart and Estrogen/Progestin Replacement Study (HERS). SETTING: Secondary analysis of a multicentre, randomised controlled clinical trial. PATIENTS: 2673 Postmenopausal women with coronary disease. MAIN OUTCOME MEASURES: AF prevalence at baseline and incident AF over a mean follow-up of 4.1 years. RESULTS: 88 Women with AF were identified: 29 at baseline and 59 during follow-up. Women with AF were significantly less likely to be taking a statin at study enrollment than those without AF (22% vs 37%, p = 0.003). Baseline statin use was associated with a 65% lower odds of having AF at baseline after controlling for age, race, history of myocardial infarction or revascularisation and history of heart failure (odds ratio 0.35, 95% confidence interval (CI) 0.13 to 0.93, p = 0.04). The risk of developing AF during the study among those free from AF at baseline, adjusted for the same covariates, was 55% less for those receiving statin treatment (hazard ratio 0.45, 95% CI 0.26 to 0.78, p = 0.004). CONCLUSIONS: Statin treatment is associated with a lower prevalence and incidence of AF after adjustment for potential confounders in postmenopausal women with coronary disease.

Postmenopausal hormone therapy and risk of stroke: The Heart and Estrogen-progestin Replacement Study (HERS).

BACKGROUND: Observational studies have shown that postmenopausal hormone therapy may increase, decrease, or have no effect on the risk of stroke. To date, no clinical trial has examined this question. To investigate the relation between estrogen plus progestin therapy and risk of stroke among postmenopausal women, we analyzed data collected from the Heart & Estrogen-progestin Replacement Study (HERS), a secondary coronary heart disease prevention trial. METHODS AND RESULTS: Postmenopausal women (n=2763) were randomly assigned to take conjugated estrogen plus progestin or placebo. Primary outcomes for these analyses were stroke incidence and stroke death during a mean follow-up of 4.1 years. The number of women with strokes was compared with the number of women without strokes. A total of 149 women (5%) had 1 or more strokes, 85% of which were ischemic, resulting in 26 deaths. Hormone therapy was not significantly associated with risk of nonfatal stroke (relative hazard [RH] 1.18; 95% CI 0.83 to 1.66), fatal stroke (RH 1.61; 95% CI 0.73 to 3.55), or transient ischemic attack (RH 0.90; 95% CI 0.57 to 1.42). Independent predictors of stroke events included increasing age, hypertension, diabetes, current cigarette smoking, and atrial fibrillation. Black women were at increased risk compared with white women, and unexpectedly, body mass index was inversely associated with stroke risk. CONCLUSIONS: Hormone therapy with conjugated equine estrogen and progestin had no significant effect on the risk for stroke among postmenopausal women with coronary disease.

Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors.

OBJECTIVE: To assess the effects of hormone therapy on urinary tract infection frequency and to examine potential risk factors. METHODS: We used data from the Heart and Estrogen/Progestin Replacement Study, a randomized, blinded trial of the effects of hormone therapy on coronary heart disease events among 2763 postmenopausal women aged 44-79 with established coronary heart disease. Participants were randomly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate or placebo and followed for a mean of 4.1 years. History of physician-diagnosed urinary tract infections and risk factors were assessed by self-report at baseline and each annual visit. RESULTS: Urinary tract infection frequency was higher in the group randomized to hormone treatment, although the difference was not statistically significant (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.99, 1.37). Statistically significant risk factors for urinary tract infections in multivariable analysis included: women with diabetes on treatment (insulin OR 1.81, 95% CI 1.40, 2.34), oral medications OR 1.44, 95% CI 1.09, 1.90), poor health (OR 1.34, 95% CI 1.14, 1.57), childbirth (OR 1.38, 95% CI 1.00, 1.90), vaginal itching (OR 1.63, 95% CI 1.07, 2.50), vaginal dryness (OR 1.30, 95% CI 1.04, 1.67), and urge incontinence (OR 1.51, 95% CI 1.30, 1.75). Urinary tract infections in the previous year were strongly associated with a single urinary tract infection (OR 7.00, 95% CI 5.91, 8.29) as well as multiple urinary tract infections (OR 18.51, 95% CI 14.27, 24.02). CONCLUSIONS: Oral hormone therapy did not reduce frequency of urinary tract infections. Potentially modifiable risk factors in postmenopausal women are different from those in younger women, and include diabetes, vaginal symptoms, and urge incontinence.

Estrogens should not be initiated for the secondary prevention of coronary artery disease: a debate.

Randomized controlled clinical trials investigating disease outcomes provide the best evidence to guide clinical practice. In the case of coronary artery disease (CAD), the only major clinical trial that has been completed does not support the epidemiological and pathophysiological evidence that estrogen is a cardioprotective agent. In the Heart and Estrogen/progestin Replacement Study (HERS), hormone replacement therapy (HRT) was of no overall benefit in the secondary prevention of CAD events in postmenopausal women. In addition, HRT was associated with a threefold increase in thromboembolic events. Based on the clinical trial evidence, estrogen therapy should not be initiated for the secondary prevention of CAD.

Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause.

CONTEXT: Lipoprotein(a) [Lp(a)] has been identified as an independent risk factor for coronary heart disease (CHD) events. However, few data exist on the clinical importance of Lp(a) lowering for CHD prevention. Hormone therapy with estrogen has been found to lower Lp(a) levels in women. OBJECTIVE: To determine the relationships among treatment with estrogen and progestin, serum Lp(a) levels, and subsequent CHD events in postmenopausal women. DESIGN AND SETTING: The Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled secondary prevention trial conducted from January 1993 through July 1998 with a mean follow-up of 4.1 years at 20 centers. PARTICIPANTS: A total of 2763 postmenopausal women younger than 80 years with coronary artery disease and an intact uterus. Mean age was 66.7 years. INTERVENTION: Participants were randomly assigned to receive either conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in 1 tablet daily (n = 1380), or identical placebo (n = 1383). MAIN OUTCOME MEASURES: Lipoprotein(a) levels and CHD events (nonfatal myocardial infarction and CHD death). RESULTS: Increased baseline Lp(a) levels were associated with subsequent CHD events among women in the placebo arm. After multivariate adjustment, women in the second, third, and fourth quartiles of baseline Lp(a) level had relative hazards (RHs) (compared with the first quartile) of 1.01 (95% confidence interval [CI], 0.64-1.59), 1.31 (95% CI, 0.85-2.04), and 1.54 (95% CI, 0.99-2.39), respectively, compared with women in the lowest quartile (P for trend = .03). Treatment with estrogen and progestin reduced mean (SD) Lp(a) levels significantly (-5.8 [15] mg/dL) (-0.20 [0.53] micromol/L) compared with placebo (0.3 [17] mg/dL) (0.01 [0.60] micromol/L) (P<.001). In a randomized subgroup comparison, women with low baseline Lp(a) levels had less benefit from estrogen and progestin than women with high Lp(a) levels; the RH for women assigned to estrogen and progestin compared with placebo were 1.49 (95% CI, 0.97-2.26) in the lowest quartile and 1.05 (95% CI, 0.67-1.65), 0.78 (0.52-1.18), and 0.85 (0.58-1.25) in the second, third, and fourth quartiles, respectively (P for interaction trend = .03). CONCLUSIONS: Our data suggest that Lp(a) is an independent risk factor for recurrent CHD in postmenopausal women and that treatment with estrogen and progestin lowers Lp(a) levels. Estrogen and progestin therapy appears to have a more favorable effect (relative to placebo) in women with high initial Lp(a) levels than in women with low levels. This apparent interaction needs confirmation in other trials.

Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study.

BACKGROUND: Oral contraceptive use increases risk for venous thromboembolism, but data on the effect of postmenopausal hormone therapy are limited. OBJECTIVE: To determine the effect of therapy with estrogen plus progestin on risk for venous thromboembolic events in postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 20 clinical centers in the United States. PARTICIPANTS: 2763 postmenopausal women younger than 80 years of age (mean age, 67 years) who had coronary heart disease but no previous venous thromboembolism and had not had a hysterectomy. INTERVENTION: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in one tablet (n = 1380) or placebo that was identical in appearance (n = 1383). MEASUREMENTS: Documented deep venous thrombosis or pulmonary embolism. RESULTS: During an average of 4.1 years of follow-up, 34 women in the hormone therapy group and 13 in the placebo group experienced venous thromboembolic events (relative hazard, 2.7 [95% CI, 1.4 to 5.0] [P = 0.003]; excess risk, 3.9 per 1000 woman-years [CI, 1.4 to 6.4 per 1000 woman-years]; number needed to treat for harm, 256 [CI, 157 to 692]). In multivariate analysis, the risk for venous thromboembolism was increased among women who had lower-extremity fractures (relative hazard, 18.1 [CI, 5.4 to 60.4]) or cancer (relative hazard, 3.9 [CI, 1.6 to 9.4]) and for 90 days after inpatient surgery (relative hazard, 4.9 [CI, 2.4 to 9.8]) or nonsurgical hospitalization (relative hazard, 5.7 [CI, 3.0 to 10.8]). Risk was decreased with aspirin (relative hazard, 0.5 [CI, 0.2 to 0.8]) or statin use (relative hazard, 0.5 [CI, 0.2 to 0.9]). CONCLUSIONS: Postmenopausal therapy with estrogen plus progestin increases risk for venous thromboembolism in women with coronary heart disease. This risk should be considered when the risks and benefits of therapy are being weighed.

Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.

OBJECTIVES: To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older. SUBJECTS AND METHODS: A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 1996. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit. RESULTS: The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5% among the men and 5.9% among the women; these figures increased over the next 6 years to 8.1% and 10.0%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9% of all participants in 1989-1990 to 7.5% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy. CONCLUSIONS: Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy.

Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group.

CONTEXT: Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials. OBJECTIVE: To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease. DESIGN: Randomized, blinded, placebo-controlled secondary prevention trial. SETTING: Outpatient and community settings at 20 US clinical centers. PARTICIPANTS: A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years. INTERVENTION: Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n = 1380) or a placebo of identical appearance (n = 1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years. MAIN OUTCOME MEASURES: The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered. RESULTS: Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38). CONCLUSIONS: During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue.

Heart and Estrogen/progestin Replacement Study (HERS): design, methods, and baseline characteristics.

The Heart and Estrogen/progestin Replacement Study (HERS) is a randomized, double-blind, placebo-controlled trial designed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease (CHD) events in women. The participants are postmenopausal women with a uterus and with CHD as evidenced by prior myocardial infarction, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or other mechanical revascularization or at least 50% occlusion of a major coronary artery. Between February 1993 and September 1994, 20 HERS centers recruited and randomized 2763 women. Participants ranged in age from 44 to 79 years, with a mean age of 66.7 (SD 6.7) years. Most participants were white (89%), married (57%), and had completed high school or some college (80%). As expected, the prevalence of coronary risk factors was high: 62% were past or current smokers, 59% had hypertension, 90% had serum LDL-cholesterol of 100 mg/dL or higher, and 23% had diabetes. Each woman was randomly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo. Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events (CHD death and nonfatal myocardial infarction). We will also assess other major CHD endpoints, including revascularization and hospitalization for unstable angina. The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo. The trial was designed to have power greater than 90% to detect a 35% reduction in the incidence of CHD events, assuming a 50% lag in effect for 2 years and a 5% annual event rate in the placebo group. The design, analysis, and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California, San Francisco. HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events.

Ten-year trends in cigarette smoking among young adults, 1986-1996: the CARDIA study. Coronary Artery Risk Development In Young Adults.

PURPOSE: To calculate ten-year smoking trends in a longitudinal cohort of young adults, and to characterize trends by race, sex, education, and birth cohort. METHODS: Data on cigarette smoking have been collected for ten years (1986-1996) from 5115 black and white men and women, aged 18-30 years, participating in the Coronary Artery Risk Development In Young Adults (CARDIA) study. Regression analysis adjusting for intra-person correlation over time and weighting for factors affecting follow-up was used to estimate change in smoking rates. RESULTS: Overall, smoking rates declined in white women (-0.50%/year, p < 0.001) and white men (-0.24%/year, p = 0.03). Rates remained stable in black women and increased in black men (0.37%/year, p = 0.01). Declining rates were generally observed in white women of all educational levels and birth cohorts and in several subgroups of white men. Increasing rates among black men could be attributed primarily to increasing rates in the youngest birth cohort. Among black men and women, prevalence of smoking in 1986 was considerably lower in the youngest birth cohort compared to the oldest; however, the increasing rates of change in smoking rates observed among the youngest birth cohorts (and decreasing rates in the oldest) lessened the disparity in prevalence rates across birth cohorts by 1996. Smoking initiation rates were highest among black men; cessation rates were highest among white women. CONCLUSIONS: These findings confirm that declines in smoking prevalence are not occurring across all groups, and reveal populations in special need of targeted interventions, particularly young black men.

Reduced cholesterol is associated with recent minor illness: the CARDIA Study. Coronary Artery Risk Development in Young Adults.

Lower levels of plasma total cholesterol have been observed during severe infection, but it is not known whether the minor illnesses encountered in the general population are also associated with reduced cholesterol. This paper examines the relation between minor illness and plasma lipids, using 7- and 10-year follow-up data from more than 3,000 generally healthy participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. At both 7 and 10 years, approximately 8.5% of participants stated they had been "ill with cold, flu, fever, or vomiting in the past 24 hours." In both cross-sectional and longitudinal analyses, the plasma total cholesterol was about 5 mg/dl lower (p < 0.006) and high density lipoprotein cholesterol about 1.2 mg/dl lower (p < 0.12) in those who reported minor illness than in those who did not. Plasma triglycerides did not vary with minor illness. The authors conclude that reductions in plasma total, low density, and high density lipoprotein cholesterol mark an acute phase response even during minor illness. These reductions may bias surveys over a limited geographic area during a short period because the proportion with minor illness may vary locally. Because this effect should be stronger with more precise illness diagnosis, clinicians should avoid making measurements for cholesterol management when illness may alter plasma lipid levels and the resulting decisions.

Estrogen replacement therapy and mortality among older women. The study of osteoporotic fractures.

BACKGROUND: Most previous studies of estrogen replacement therapy (ERT) and mortality have focused on younger women. Recently, it has been suggested that the effect of ERT on mortality may represent a "healthy-user" effect, ie, those with healthier lifestyles having a greater likelihood of receiving ERT. METHODS: Nine thousand seven hundred four women, 65 years or older, participated; 1258 (14.1%) reported current use of ERT for at least 1 year at entry. During an average follow-up of 6.0 years, 1054 women (11.8%) died. RESULTS: After adjusting for multiple variables, mortality rate was lower among current (relative risk [RR], 0.69; 95% confidence interval [CI], 0.54-0.87) and past users (RR, 0.79; 95% CI, 0.66-0.95), mainly due to reductions in deaths due to cardiovascular disease. The protective effect of ERT was greatest among women younger than 75 years (RR, 0.55; 95% CI, 0.40-0.76) compared with women from 75 to 84 years of age (RR, 0.93; 95% CI, 0.62-1.41) and 85 years or older (RR, 1.33; 95% CI, 0.43-4.12). The RR for overall mortality was 0.95 (95% CI, 0.68-1.32) among short-term users (1-9 years) compared with 0.55 (95% CI, 0.40-0.75) among long-term users (> or = 10 years). Deaths considered unrelated to ERT tended also to be reduced in current users younger than 75 years (RR, 0.72; 95% CI, 0.49-1.06) and current long-term users (RR, 0.75; 95% CI, 0.51-1.10). CONCLUSIONS: Estrogen replacement therapy is associated with lower overall mortality rates and reduced deaths due to cardiovascular disease. Women using ERT had healthier lifestyles, and the risk for death thought to be unrelated to ERT also tended to be lower in ERT users, suggesting in part a healthy-user effect.

Adherence to National Cholesterol Education Program Treatment goals in postmenopausal women with heart disease. The Heart and Estrogen/Progestin Replacement Study (HERS). The HERS Research Group.

OBJECTIVES: To determine the proportion of volunteer women with established heart disease who have low-density lipoprotein cholesterol (LDL-C) levels at or below the National Cholesterol Education Program Adult Treatment Panel goals and to determine what factors are associated with levels above goal or not receiving lipid-lowering medication when indicated. DESIGN: Cross-sectional measurement of lipids and lipoproteins, blood pressure, height, weight, and other demographic and cardiovascular risk factors in 2763 postmenopausal women with heart disease. SETTING: At 18 centers throughout the United States, participants were recruited by means of lists of women with coronary heart disease from coronary units and catheterization laboratories, direct mail to age-eligible women, and advertisements. PATIENTS: Mean age of the cohort was 66.7 years (range, 44-79 years) and the distribution by race/ethnicity was 88.7% white, 7.9% African American, 2.0% Hispanic/Latina, 0.8% Asian/Pacific Islander, and 0.7% other. INTERVENTION: We report cross-sectional analysis of the cohort at baseline. OUTCOME MEASURES: We measured the frequency of achieving 1988 and 1993 Adult Treatment Panel treatment goals, and of being on a regimen of lipid-lowering medication. RESULTS: Although 47% of participants were taking a lipid-lowering medication, 63% did not meet the 1988 treatment goal of LDL-C level less than 3.4 mmol/L (130 mg/dL) and 91% did not meet the 1993 goal of LDL-C level less than 2.6 mmol/L (100 mg/dL). Factors independently associated with achieving the earlier goal were use of lipid-lowering medication, marital status, education, body mass index, exercise, hypertension, diabetes, gallbladder disease, and first diagnosis of coronary heart disease after 1990. Failure to use lipid-lowering medication was associated with age, being African American, marital status, body mass index, lack of exercise, alcohol consumption, current smoking, and first diagnosis of coronary heart disease before 1985. CONCLUSION: The majority of women enrolled in the trial had LDL-C levels that significantly exceeded the treatment goals set by the 1988 and 1993 Adult Treatment Panel guidelines. Better implementation of these guidelines among women with coronary disease would be highly desirable.

Changes in HIV-related behaviors among heterosexual alcoholics following addiction treatment.

In order to measure changes in HIV-related behaviors among heterosexual alcoholics following treatment, we conducted a prospective cohort study of 700 self-identified alcoholics recruited from five public alcohol treatment centers, all of which included HIV risk-reduction counseling. Respondents underwent an HIV antibody test and interviewer-administered questionnaire at entry to alcohol treatment and after a mean of 13 months later. Compared to baseline, at follow-up there was an overall 26% reduction in having sex with an injection-drug-using partner (23% versus 32%, P < .001) and a 58% reduction in the use of injection drugs (15% versus 37%, P < .001), along with smaller improvements in other behaviors. Respondents also showed a 77% improvement in consistent condom use with multiple sexual partners (35% versus 20%, P < .01) and a 23% improvement in partner screening (71% versus 57%, P < .001). Respondents who remained abstinent showed substantially greater improvement than those who continued to drink.