Effect of statin dose on incidence of atrial fibrillation: data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials.

BACKGROUND: Inflammation has been suggested as a factor in the initiation and maintenance of atrial fibrillation (AF). Several observational studies have suggested that statins, presumably through their anti-inflammatory properties, decrease the risk of AF. METHODS: We analyzed 2 large, randomized trials, PROVE IT-TIMI 22 and phase Z of the A to Z trial, which compared lower- versus higher-intensity statin therapy to evaluate whether higher-intensity statin therapy lowered the risk of AF onset during the 2 years of follow-up. We hypothesized that higher-intensity statin therapy would decrease the risk of AF when compared to lower-intensity statin therapy. From each trial, patients experiencing the onset of AF during follow-up were identified from the adverse event reports. RESULTS: Neither study showed a decreased AF risk with higher-dose statin. In PROVE IT-TIMI 22, 2.9% versus 3.3% in the high- versus standard-dose statin therapy, respectively, experienced the onset of AF over 2 years (OR 0.86, 95% CI 0.61-1.23, P = .41). In A to Z, rates were 1.6% versus 0.99%, respectively (OR 1.58, 95% CI 0.92-2.70, P = .096). In both trials, C-reactive protein levels (plasma or serum) tended to be higher among patients experiencing the onset of AF. CONCLUSION: Our randomized comparison among 8659 patients found that higher-dose statin therapy did not reduce the short term incidence of AF among patients after acute coronary syndromes when compared with standard dose statin treatment.

Unanswered ethical and scientific questions for trials of invasive interventions for coronary disease: The case of single vessel disease.

Trials in the 1990s demonstrated that medical therapy is as effective as invasive therapies for treating single-vessel coronary disease. Yet more recent studies enrolling patients with this condition have focused on evaluating only invasive approaches, namely, stenting versus coronary artery bypass surgery. Several ethical and scientific questions remain unanswered regarding the conduct of these later trials. Were they justified? Why wasn't a medical therapy arm included? Were subjects informed about the availability of medical therapy as an equivalent option? Was optimized medical therapy given prior to randomization? The absence of clear answers to these questions raises the possibility of serious bias in favor of invasive interventions. Considering that medical therapy is underutilized in patients with coronary disease, efforts should focus more on increasing utilization of medical therapy and proper selection of noninvasive interventions.

Long-term outcomes of optimized medical management of outpatients with stable coronary artery disease.

The objective of this study was to assess long-term clinical outcomes and their correlates in medically managed outpatients with stable angina pectoris, healed myocardial infarction (MI), or documented asymptomatic coronary artery disease (CAD). Management strategy emphasized maximally tolerated medical therapy and modification of coronary risk factors. Referral to invasive coronary interventions followed stricter criteria than standard published guidelines. Primary study outcomes were all-cause mortality or nonfatal myocardial infarction. Secondary study outcomes included cardiac death, unstable angina, or coronary revascularization. A total of 693 men and women with proved CAD (mean age 67 years at entry, 85% men, 41% with history of MI) were enrolled. The annual incidence of nonfatal MI, cardiac mortality, and total mortality was 2.2%, 0.8%, and 1.4%, respectively, during an average follow-up of 4.6 years. Coronary revascularization was performed in 24% of subjects; unstable or progressive anginal symptoms were the most common reasons for revascularization. In patients with documented stable CAD, a management strategy based on intensive medical therapy and modification of established coronary risk factors was associated with excellent long-term outcomes. Thus, coronary interventions can be safely delayed until clinical instability ensues, without increased risk of MI or death. This treatment approach represents a viable alternative to invasive strategies.

Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease.

Atrial fibrillation (AF) is prevalent in the elderly, in patients with hypertension, and in patients with coronary artery disease (CAD). We hypothesized that statin therapy might be effective in preventing AF in patients with CAD and examined this hypothesis in a sample of patients with chronic stable CAD without AF, followed prospectively at a large outpatient cardiology practice. The association between statin use and the risk of developing AF was examined univariately and then with adjustment for potential confounding factors. Four hundred forty-nine men and women between the ages of 40 and 87 years were followed for an average of 5 years. Fifty-two patients (12%) developed AF during follow-up. Statin therapy was used by 59% of the patients during the study period and was associated with a significantly reduced risk of developing AF (crude odds ratio, 0.48, 95% confidence interval 0.28 to 0.83). This association remained significant after adjustment for potential confounders, including age, hypertension, left ventricular systolic function, occurrence of heart failure or acute ischemic events, and baseline cholesterol and changes in cholesterol levels (adjusted odds ratio 0.37, 95% confidence interval 0.18 to 0.76). Use of statins in patients with chronic stable CAD appears to be protective against AF. The underlying mechanism for this effect is unknown but appears to be independent of the reduction in serum cholesterol levels.

Brain natriuretic peptide is elevated in outpatients with atrial fibrillation.

Brain natriuretic peptide (BNP) levels were measured in 72 outpatients with chronic atrial fibrillation (AF) and in 49 control patients without AF. BNP levels were significantly higher in patients with AF (median value 131 pg/ml) than without AF (median value 49 pg/ml; p <0.001), and remained significantly higher after controlling for demographic and clinical variables.

Long-term statin use and psychological well-being.

OBJECTIVES: We sought to study the effect of long-term statin use on psychometric measures in an adult population with underlying coronary artery disease (CAD). BACKGROUND: Previous studies have suggested associations between cholesterol lowering and psychological well-being. METHODS: Study subjects were recruited from an outpatient cardiology clinic. Psychological well-being was assessed at baseline and annually during follow-up. The exposure of interest was long-term statin use and the outcomes of interest were depression, anxiety, and hostility. We estimated the odds ratios (ORs) and 95% confidence intervals (CI) that represented the strength of association between statin use (vs. no use of any cholesterol-lowering drug) and the risk of having abnormal depression, anxiety, and hostility scores. RESULTS: Study subjects had an average follow-up of four years and maximum of seven years. Comparing the 140 patients who had continuous use of statins with the 231 patients who did not use any cholesterol-lowering drugs, statin use was associated with lower risk of abnormal depression scores (OR 0.63, 95% CI 0.43 to 0.93), anxiety (OR 0.69, 95% CI 0.47 to 0.99), and hostility (OR 0.77, 95% CI 0.58 to 0.93) after adjustment for the propensity for statin use and potential confounders. The beneficial psychological effects of the statins appeared to be independent of the drugs' cholesterol-lowering effects. CONCLUSIONS: Long-term use of statins among patients with CAD appeared to be associated with reduced risk of anxiety, depression, and hostility.

Two-decade-long trends (1975-1997) in the incidence, hospitalization, and long-term death rates associated with complete heart block complicating acute myocardial infarction: a community-wide perspective.

BACKGROUND: The purpose of this community-wide study was to describe a >2-decade-long experience (1975-97) in the incidence and death rates associated with complete heart block (CHB) in patients with acute myocardial infarction (AMI). Limited population-based data exist describing recent, and changes with time therein, incidence and case-fatality rates associated with CHB complicating AMI. METHODS: We conducted an observational study of 9082 metropolitan Worcester, Mass, residents (1990 census = 437,000) hospitalized with validated AMI in all greater Worcester hospitals during 11 1-year periods between 1975 and 1997. RESULTS: Overall, CHB developed in 5.0% of patients with AMI. The incidence rates of CHB declined in the periods studied (6.0% in 1975/78 vs 3.1% in 1997). Declines in the occurrence of CHB were noted in patients with anterior or inferior/posterior MI. These trends remained after adjustment for other factors that might affect the risk of CHB. Patients in whom CHB developed experienced significantly higher hospital death rates than patients in whom CHB did not develop (46.8% vs 14.6%). However, improving trends in the hospital survival rate of patients with CHB were observed between 1975/78 (47.4% surviving) and 1997 (61.3% surviving). Patients in whom CHB developed during hospitalization were not at increased risk for dying after hospital discharge. CONCLUSIONS: Our findings indicate that the incidence of CHB complicating AMI has declined with time. The hospital prognosis of patients in whom CHB developed has improved, but these patients remain at an increased risk of hospital mortality. The long-term prognosis of patients with inferior MI and CHB is similar to that of patients in whom CHB did not develop. Patients with anterior MI and CHB may be at an increased risk of long-term mortality.