Wearable Cardioverter-Defibrillator after Myocardial Infarction.

BACKGROUND: Despite the high rate of sudden death after myocardial infarction among patients with a low ejection fraction, implantable cardioverter-defibrillators are contraindicated until 40 to 90 days after myocardial infarction. Whether a wearable cardioverter-defibrillator would reduce the incidence of sudden death during this high-risk period is unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients with acute myocardial infarction and an ejection fraction of 35% or less to receive a wearable cardioverter-defibrillator plus guideline-directed therapy (the device group) or to receive only guideline-directed therapy (the control group). The primary outcome was the composite of sudden death or death from ventricular tachyarrhythmia at 90 days (arrhythmic death). Secondary outcomes included death from any cause and nonarrhythmic death. RESULTS: Of 2302 participants, 1524 were randomly assigned to the device group and 778 to the control group. Participants in the device group wore the device for a median of 18.0 hours per day (interquartile range, 3.8 to 22.7). Arrhythmic death occurred in 1.6% of the participants in the device group and in 2.4% of those in the control group (relative risk, 0.67; 95% confidence interval [CI], 0.37 to 1.21; P=0.18). Death from any cause occurred in 3.1% of the participants in the device group and in 4.9% of those in the control group (relative risk, 0.64; 95% CI, 0.43 to 0.98; uncorrected P=0.04), and nonarrhythmic death in 1.4% and 2.2%, respectively (relative risk, 0.63; 95% CI, 0.33 to 1.19; uncorrected P=0.15). Of the 48 participants in the device group who died, 12 were wearing the device at the time of death. A total of 20 participants in the device group (1.3%) received an appropriate shock, and 9 (0.6%) received an inappropriate shock. CONCLUSIONS: Among patients with a recent myocardial infarction and an ejection fraction of 35% or less, the wearable cardioverter-defibrillator did not lead to a significantly lower rate of the primary outcome of arrhythmic death than control. (Funded by the National Institutes of Health and Zoll Medical; VEST ClinicalTrials.gov number, NCT01446965 .).

Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment.

BACKGROUND: Use of 3-hydroxyl-3-methylglutaryl-3 coenzyme A reductase (HMGCR) inhibitors, or statins, reduces cardiovascular disease risk by lowering plasma low-density lipoprotein cholesterol (LDL-C) concentrations. However, LDL-C response is variable and influenced by many factors, including racial ancestry, with attenuated response in blacks compared with whites. We hypothesized that single nucleotide polymorphisms in the gene encoding HMGCR, a rate-limiting enzyme in cholesterol synthesis and the direct enzymatic target of statins, contribute to variation in statin response. METHODS AND RESULTS: Genomic resequencing of HMGCR in 24 blacks and 23 whites identified 79 single nucleotide polymorphisms. Eleven single nucleotide polymorphisms were selected to tag common linkage disequilibrium clusters. These single nucleotide polymorphisms and the common haplotypes inferred from them were tested for association with plasma LDL-C and LDL-C response to simvastatin treatment (40 mg/d for 6 weeks) in 326 blacks and 596 whites. Black carriers of H7 and/or H2 had significantly lower baseline LDL-C (P=0.0006) and significantly attenuated LDL-C response compared with black participants who did not carry either haplotype as measured by absolute response (-1.23+/-0.04 mmol/L, n=209, versus -1.45+/-0.06 mmol/L, n=117; P=0.0008) and percent response (-36.9+/-1.0% versus -40.6+/-1.3%; P=0.02), but no haplotype effect was observed in whites. Percent LDL-C response was lowest in carriers of both H2 and H7, all but one of whom were black (-28.2+/-4.9%, n=12 H2+H7 carriers, versus -41.5+/-0.5%, n=650 H2/H7 noncarriers; P=0.001). LDL-C responses in H7 and/or H2 noncarriers were indistinguishable between blacks and whites. CONCLUSIONS: HMGCR gene polymorphisms are associated with reduced plasma LDL-C and LDL-C response to simvastatin, and these effects are most evident in blacks.

Sustained-release bupropion for hospital-based smoking cessation: a randomized trial.

INTRODUCTION: Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a general population of hospitalized smokers. METHODS: We enrolled 85 smokers in a hospital-based randomized smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center. A total of 42 participants received a 7-week course of sustained-release bupropion and 43 participants received placebo. All participants received cognitive-behavioral counseling. We screened 14,997 patients, of whom 25% were current smokers. Of the 536 smokers who met the entry criteria, 451 opted not to enroll. We determined on-medication, end-of-medication, 3-month, and 6-month smoking cessation rates. RESULTS: At the end of 7 weeks of drug treatment, self-reported quit rates were equivalent in the bupropion and placebo arms, 37% versus 33%, respectively (p = .82). The validated quit rates for the bupropion and placebo groups were 27% versus 29%, respectively (p = 1.00). At 6 months, the self-reported quit rates were 29% in the bupropion group and 41% in the placebo group (p = .36). In a comparison of 6-month quit rates, validated either by salivary cotinine or by spousal proxy, we found nonsignificantly higher quit rates in the placebo group than in the bupropion group, 31% versus 15% (p = .12). DISCUSSION: The addition of sustained-release bupropion to counseling did not increase quit rates, but the study was underpowered. Because of the secular trend toward shorter hospital stays, recruitment was very difficult, raising questions regarding the feasibility of future hospital-based smoking cessation trials and interventions.

Differential effects of ramipril on ambulatory blood pressure in African Americans and Caucasians.

BACKGROUND: On average, angiotensin-converting enzyme inhibitors produce less office blood-pressure lowering in African Americans compared with Caucasians. Past studies did not compare daytime and nighttime ambulatory blood-pressure responses to angiotensin-converting enzyme inhibitors in African Americans and Caucasians. METHODS: We measured the office and ambulatory blood-pressure response to 8 weeks of a fixed dose of 10 mg daily of the angiotensin-converting enzyme inhibitor ramipril in a cohort of 72 African Americans and 89 Caucasians. RESULTS: Ramipril lowered age-adjusted daytime ambulatory systolic blood pressure 6 mm Hg and diastolic blood pressure 3 mm Hg less in African Americans compared with Caucasians (both P=.02). This difference persisted after adjusting for baseline blood pressure, body mass index, urine sodium and potassium, plasma aldosterone, and other covariates. Despite the difference in mean response, there was a 72% overlap in daytime blood-pressure response to ramipril between African Americans and Caucasians. Among Caucasians, ramipril lowered systolic blood pressure 2 mm Hg less during nighttime compared with daytime, whereas among African Americans, blood pressure lowering was equivalent during day and night. Nighttime blood-pressure response to ramipril did not differ significantly between African Americans and Caucasians. CONCLUSIONS: Ramipril was more effective in lowering daytime blood pressure in Caucasians compared with African Americans, but appreciable differences in response did not persist at night. Despite the small difference in mean response between groups, the majority of African Americans and Caucasians had a similar blood-pressure response to a fixed dose of ramipril.

Hypnosis for Smoking Relapse Prevention: A Randomized Trial.

The purpose of this study was to determine whether hypnosis would be more effective than standard behavioral counseling in helping smokers to remain abstinent. A total of 140 current smokers were enrolled in a randomized controlled smoking cessation trial at an urban Veterans Affairs medical center. Participants (n = 102) who were able to quit for at least 3 days received either a hypnosis or behavioral relapse prevention intervention. Both relapse prevention interventions consisted of two 60 min face-to-face sessions and four 20 min follow-up phone calls (two phone calls per week). At 26 weeks, the validate\d point-prevalence quit rate was 35% for the hypnosis group and 42% for the behavioral counseling group (relative risk = 0.85; 95% confidence interval: 0.52-1.40). At 52 weeks, the validated quit rate was 29% for the hypnosis group and 28% for the behavioral group (relative risk  = 1.03; 95% confidence interval: 0.56-1.91). It was concluded that hypnosis warrants further investigation as an intervention for facilitating maintenance of quitting.

Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study.

Although statins are effective lipid-lowering agents, the phenotypic and demographic predictors of such lowering have been less well examined. We enrolled 944 African-American and white men and women who completed an open-label, 6-week pharmacogenetics trial of 40 mg of simvastatin. The phenotypic and demographic variables were examined as predictors of the change in lipids and lipoproteins using linear regression analysis. On average, treatment with simvastatin lowered low-density lipoprotein (LDL) cholesterol by 54 mg/dl and increased high-density lipoprotein (HDL) cholesterol by 2 mg/dl. Compared with African-Americans, whites had a 3-mg/dl greater LDL reduction and a 1-mg/dl higher HDL elevation, independent of other variables, including baseline lipoprotein levels (p <0.01). Multivariate analyses revealed moderate subgroup differences, with older participants having a larger decrease in LDL cholesterol and apolipoprotein B levels compared with younger participants (p <0.001), women having larger increases in HDL than men (p <0.01), nonsmokers having larger decreases in LDL and triglyceride levels compared with smokers (p <0.05), those with hypertension having smaller decreases in apolipoprotein B than those without hypertension (p <0.05), and those with a larger waist circumference having a diminished lowering of triglycerides in response to treatment with simvastatin (p <0.01). In conclusion, treatment with simvastatin produced favorable lipid and lipoprotein changes among all participants. The magnitude of the lipid and lipoprotein responses, however, differed among participants according to a number of phenotypic and demographic characteristics.

The relation of postmenopausal hormone therapy to serum uric acid and the risk of coronary heart disease events: the Heart and Estrogen-Progestin Replacement Study (HERS).

PURPOSE: To determine whether baseline serum uric acid (UA) levels and estrogen-progestin (E+P)-associated change in serum UA in postmenopausal women with coronary disease are associated with recurrent coronary heart disease (CHD) events. METHODS: 2763 postmenopausal women enrolled in the Heart and Estrogen-Progestin Replacement Study (HERS) were randomly assigned to take conjugated E+P or placebo in a secondary CHD prevention study. The primary outcome for these analyses was nonfatal myocardial infarction or CHD death during a mean follow up of 4.1 years. RESULTS: The baseline serum UA for the cohort was 5.4 mg/dl and, compared with placebo, E+P on average lowered serum UA levels slightly (0.2 mg/dl) at one year of follow up (p<0.0001). Baseline serum UA levels were associated in simple proportional hazards models with CHD events; each standard deviation increase (1.3 mg/dl) was associated with a 22% increased risk of primary CHD events (p=.0001). This association, however, was no longer statistically significant after multivariable adjustment (p=0.36). There was no association between on-study change in serum UA level and any CHD outcome. CONCLUSION: Treatment with E+P lowered serum UA levels slightly, but neither baseline UA nor change in UA affected CHD risk.

Bupropion for smoking cessation: a review.

Smoking tobacco is the leading cause of preventable death. Bupropion is the only antidepressant recommended as first-line pharmacotherapy for smoking cessation. Bupropion is as effective as nicotine replacement therapy and can be used in diverse populations.

Subgroup interactions in the Heart and Estrogen/Progestin Replacement Study: lessons learned.

BACKGROUND: The Heart and Estrogen/Progestin Replacement Study (HERS) showed no overall benefit of postmenopausal hormone treatment in women with coronary heart disease (CHD). We analyzed the HERS data to determine whether there were specific subgroups of women who responded differently to treatment, either during the first year or in the overall study. METHODS AND RESULTS: In the search for significant treatment interactions, we analyzed a total of 86 subgroups defined by baseline characteristics. These included demographics and lifestyle factors, laboratory and physical examination variables, medical history and symptoms by self-report, medication use, and prior CHD history by chart review. We examined within-subgroup treatment effects for baseline variables that significantly interacted with treatment assignment. Under the null hypothesis, 4 (5%) of the 86 interactions would be expected to be nominally significant (P<0.05) by chance alone at each time point. Six of the interaction values were P<0.05 at 1 year, and 3 were P<0.05 at trial completion. The findings are discussed in the context of known mechanisms of action and prior scientific knowledge. Use of digitalis and history of myocardial infarction emerged as 2 possible modifiers of the effect of hormone therapy during the first year, and lipoprotein(a) emerged as a possible modifier during the overall study. CONCLUSIONS: Extensive post hoc analyses did not identify any subgroup of HERS participants in which postmenopausal hormone treatment was clearly beneficial or harmful, but several possibilities emerged for testing in future trials.

Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women's Health Initiative.

BACKGROUND: Antioxidant defenses are one possible mechanism for decreasing oxidative damage and its potentially negative effects on age-related bone mass. OBJECTIVE: This study cross-sectionally examined whether higher dietary intakes, total intakes, and serum concentrations of antioxidants may be associated with higher bone mineral density (BMD). DESIGN: Total hip (and subregions), spine, and total-body BMDs were measured in 11,068 women aged 50-79 y enrolled in the Women's Health Initiative Observational Study and Clinical Trial at 3 clinics. Antioxidant intakes from diet (vitamin A, retinol, beta-carotene, vitamin C, vitamin E, and selenium) were estimated by using a self-reported food-frequency questionnaire. Antioxidants from supplements were estimated with an interviewer-administered questionnaire. A random subset (n = 379) had serum concentrations of retinol, carotenoids, and tocopherols measured. RESULTS: After adjustment for important BMD-related covariates, increasing intakes of antioxidants were not independently associated with BMD. A significant interaction effect was observed between intake of total vitamin C (lower three-fourths compared with highest one-fourth) and use of hormone therapy (HT) (P < 0.01). The beneficial effect of current HT use on femoral neck BMD appeared to be greater in women with higher concentrations of total vitamin C. This interaction was also significant for total-body (P < 0.045), spine (P = 0.03), and total-hip BMDs (P = 0.029). CONCLUSIONS: Our results do not support independent associations between dietary intake, total intake, or serum concentrations of antioxidants and BMD in women participating in the Women's Health Initiative. The extent to which HT use may interact with vitamin C intake and BMD warrants further exploration.

Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease.

Oral contraceptive use in women with factor V Leiden is associated with increased rates of venous thromboembolic events (VTEs). However, the effects of hormone replacement therapy (HRT) in postmenopausal women with factor V Leiden are not known. A nested case-control study was conducted among women with established coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio [OR](Leiden) 3.3, 95% CI 1.1 to 9.8; P=0.03). In women without the factor V Leiden mutation, risk associated with HRT use was significantly increased (OR(HRT) 3.7, 95% CI 1.4 to 9.4; P<0.01). On the other hand, in women with the factor V Leiden mutation, the estimated risk associated with HRT was increased nearly 6-fold, although the CIs were wide and included unity (OR(HRT) 5.7, 95% CI 0.6 to 53.9; P=0.13). The OR for women with the Leiden mutation who were also assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95% CI 2.7 to 72.4, P=0.0015). In women with the factor V Leiden mutation who were treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per year compared with 2.0 of 1000 per year in women without the mutation who were taking a placebo (P=0.0015). On the basis of these data, in women with coronary disease, the estimated number needed to screen for factor V Leiden to avoid an HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease.

Bupropion for smoking cessation: a randomized trial.

BACKGROUND: Bupropion hydrochloride is recommended for smoking cessation; however, there have been relatively few clinical trials examining its efficacy. METHODS: A total of 244 current smokers were enrolled in an outpatient randomized blinded smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center, San Francisco, Calif. Of the 244 participants, 121 received a 7-week course of bupropion and 123 received placebo. All participants received 2 months of transdermal nicotine replacement therapy and 3 months of cognitive-behavioral counseling. We determined on-medication treatment, end-of-medication treatment, 3-month, 6-month, and 1-year quit rates. RESULTS: During treatment with bupropion vs placebo, there was a trend toward increased quit rates among participants randomized to bupropion; the self-reported end-of-medication treatment quit rates were 64% for the bupropion group vs 57% for the placebo group (P =.23). The trend favoring bupropion persisted at 3 months of follow-up (P =.12) but was not apparent at 6 months and 1 year of follow-up (both P>.78). The 12-month quit rates, validated by either saliva cotinine or spousal proxy, were 22% in the bupropion group and 28% in the placebo group (P =.31). Based on biochemical validation, 19% of the bupropion group vs 24% of the placebo group had quit smoking by 1 year (P =.36). CONCLUSIONS: In this randomized blinded trial of mostly veteran participants, the addition of a brief 7-week bupropion trial to treatment with nicotine replacement therapy and counseling did not significantly increase smoking cessation rates.

Intensive smoking cessation counseling versus minimal counseling among hospitalized smokers treated with transdermal nicotine replacement: a randomized trial.

PURPOSE: To determine whether an intensive cognitive-behavioral intervention begun during hospitalization when combined with transdermal nicotine replacement therapy is more effective than a minimal counseling intervention combined with transdermal nicotine replacement therapy in helping inpatients to quit smoking. METHODS: A total of 223 patients who smoked were enrolled in a hospital-based randomized smoking cessation trial at the San Francisco Veterans Affairs Medical Center. One hundred and seven participants (48%) received intensive counseling and outpatient telephone follow-up; 116 participants (52%) received minimal counseling. All study participants received 2 months of transdermal nicotine replacement therapy. We determined 6-month quit rates by self-report and measured saliva cotinine levels or obtained proxy reports to confirm self-reported smoking cessation at 12 months. Analyses adjusted for baseline differences in the distribution of coronary disease. RESULTS: At 6 months, 35% (36/103) of the intensive intervention group reported quitting, compared with 21% (23/109) of the comparison group (relative risk [RR] = 1.7; 95% confidence interval [CI]: 1.1 to 2.7). At 12 months, the self-reported quit rate was 33% (33/99) in the intensive intervention group versus 20% (21/103) in the comparison group (RR = 1.7; 95% CI: 1.1 to 2.7). Based on biochemical or proxy confirmation, 29% (30/102) in the intensive intervention group versus 20% (21/107) in the comparison group quit smoking at 12 months (RR = 1.6; 95% CI: 0.96 to 2.5). CONCLUSION: Hospital-initiated smoking cessation interventions that include transdermal nicotine replacement therapy can improve long-term quit rates.

Telephone-delivered cognitive-behavioral therapy for pain management among older military veterans: a randomized trial.

This study investigated the effectiveness of telephone-delivered cognitive-behavioral therapy (T-CBT) in the management of chronic pain with older military veterans enrolled in VA primary-care clinics. We conducted a randomized clinical trial comparing T-CBT with telephone-delivered pain education (T-EDU). A total of 98 military veterans with chronic pain were enrolled in the study and randomized into one of two treatment conditions. Study participants were recruited from primary-care clinics at an urban VA medical center and affiliated VA community-based outpatient clinics (CBOCs). Pain management outcomes were measured at midtreatment (10 weeks), posttreatment (20 weeks), 3-month follow-up (32 weeks), and 6-month follow-up (46 weeks). No significant differences were found between the two treatment groups on any of the outcome measures. Both treatment groups reported small but significant increases in level of physical and mental health, and reductions in pain and depressive symptoms. Improvements in all primary outcome measures were mediated by reductions in catastrophizing. Telephone-delivered CBT and EDU warrant further study as easily accessible interventions for rural-living older individuals with chronic pain.

Expectancies regarding the interaction between smoking and substance use in alcohol-dependent smokers in early recovery.

The purpose of this study was to investigate expectancies regarding the interaction between cigarette smoking and use of alcohol among alcohol-dependent smokers in early recovery, using the Nicotine and Other Substances Interaction Expectancies Questionnaire (NOSIE). Participants were 162 veterans, 97% male, with a mean age of 50 years, enrolled in a clinical trial aimed at determining the efficacy of an intensive smoking cessation intervention versus usual care. At baseline, participants were assessed on measures of smoking behavior, abstinence thoughts about alcohol and tobacco use, symptoms of depression, and smoking-substance use interaction expectancies. In addition, biologically verified abstinence from tobacco and alcohol was assessed at 26 weeks. Participants reported that they expected smoking to have less of an impact on substance use than substance use has on smoking (p < .001). Severity of depressive symptoms was significantly associated with the expectancy that smoking provides a way of coping with the urge to use other substances (p < .01). The expectation that smoking increases substance urges/use was predictive of prospectively measured and biologically verified abstinence from smoking at 26 weeks (p < .03). The results add to our knowledge of smoking-substance use interaction expectancies among alcohol-dependent smokers in early recovery and will inform the development of more effective counseling interventions for concurrent alcohol and tobacco use disorders.

Intensive intervention for alcohol-dependent smokers in early recovery: a randomized trial.

INTRODUCTION: The purpose of this study was to investigate the efficacy of an intensive tobacco cessation intervention for alcohol-dependent smokers in early recovery. METHODS: A total of 162 alcohol-dependent smokers were randomized to either intensive intervention for smoking cessation or usual care. The intensive intervention consisted of 16 sessions of individual cognitive behavior therapy (CBT) and combination nicotine replacement therapy that lasted 26 weeks. Usual care involved referral to a free-standing smoking cessation program that provided smoking cessation counseling of varying duration and guideline-concordant medications. The primary cessation outcome was verified 7-day point prevalence abstinence (PPA) at 12, 26, 38, and 52 weeks. RESULTS: At 12 and 26 weeks, the verified 7-day point-prevalence quit rate was significantly higher for the intensive intervention group than for the usual care group (both p=0.03). However, the quit rates for the two treatment groups were not significantly different at 38 or 52 weeks. Verified 30-day alcohol abstinence rates were not significantly different for the two treatment groups at any of the follow-up assessments. CONCLUSIONS: The intensive smoking cessation intervention yielded a higher short-term smoking quit rate without jeopardizing sobriety. A chronic care model might facilitate maintenance of smoking cessation during the first year of alcohol treatment and perhaps for longer periods of time. It is hoped that studies such as this will inform the development of more effective interventions for concurrent alcohol and tobacco use disorders.