OBJECTIVE: To determine the efficacy of healthcare information technology (HIT) interventions in improving adherence. STUDY DESIGN: Systematic search of randomized controlled trials of HIT interventions to improve medication adherence in cardiovascular disease or diabetes. METHODS: Interventions were classified as 1-way patient reminder systems, 2-way interactive systems, and systems to enhance patient-provider interaction. Studies were subclassified into those with and without real-time provider feedback. Cohen's d effect sizes were calculated to assess each intervention's magnitude of effectiveness. RESULTS: We identified 7190 articles, only 13 of which met inclusion criteria. The majority of included studies (54%, 7 studies) showed a very small ES. The effect size was small in 15%, large in 8%, and was not amenable to calculation in the remainder. Reminder systems were consistently effective, showing the largest effect sizes in this review. Education/counseling HIT systems were less successful, as was the addition of realtime adherence feedback to healthcare providers. Interactive systems were rudimentary and not integrated into electronic health records; they exhibited very small effect sizes. Studies aiming to improve patient-provider communication also had very small effect sizes. CONCLUSIONS: There is a paucity of data about HIT's efficacy in improving adherence to medications for cardiovascular disease and diabetes, although simple patient reminder systems appear effective. Future studies should focus on more sophisticated interactive interventions that expand the functionality and capabilities of HIT and better engage patients in care.

OBJECTIVE: To determine the optimal modes of delivery for interventions to improve adherence to cardiovascular medications. STUDY DESIGN: Systematic review. METHODS: We conducted systematic searches of English-language, peer-reviewed publications in MEDLINE and EMBASE, 1966 through December 31, 2008. We selected randomized controlled trials of interventions to improve adherence to medications for preventing or treating cardiovascular disease or diabetes. Articles were classified based on mode of delivery of the main intervention as (1) person-independent interventions (mailed, faxed, or hand distributed; or delivered via electronic interface) or (2) person-dependent interventions (nonautomated phone calls, in-person interventions). RESULTS: We identified 6550 articles. Of these, 168 were reviewed in full and 51 met inclusion criteria. Among person-independent interventions (56% successful), electronic interventions were most successful (67%). Among person-dependent interventions (52% successful), phone calls showed low success rates (38%). In-person interventions at hospital discharge were more effective (67%) than clinic interventions (47%). In-person pharmacist interventions were effective when held in a pharmacy (83% successful), but were less effective in clinics (38%). CONCLUSIONS: Future medication adherence studies should explore new electronic approaches and in-person interventions at the site of medication distribution. Identifying times of increased patient receptivity to the adherence message such as hospital discharge also will be important.

Background While the role of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) in secondary prevention of cardiovascular (CV) events and mortality is established, their value for primary prevention is less clear. To clarify the role of statins for patients without CV disease, we performed a meta-analysis of randomized controlled trials (RCTs). Methods MEDLINE, EMBASE, Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. We included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model. Results Seven trials with 42 848 patients were included. Ninety percent had no history of CV disease. Mean follow-up was 4.3 years. Statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = .02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively. Statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). No significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed. Conclusion In patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality.

CONTEXT: Cardiac tamponade is a state of hemodynamic compromise resulting from cardiac compression by fluid trapped in the pericardial space. The clinical examination may assist in the decision to perform pericardiocentesis in patients with cardiac tamponade diagnosed by echocardiography. OBJECTIVE: To systematically review the accuracy of the history, physical examination, and basic diagnostic tests for the diagnosis of cardiac tamponade. DATA SOURCES: MEDLINE search of English-language articles published between 1966 and 2006, reference lists of these articles, and reference lists of relevant textbooks. STUDY SELECTION: We included articles that compared aspects of the clinical examination to a reference standard for the diagnosis of cardiac tamponade. We excluded studies with fewer than 15 patients. Of 787 studies identified by our search strategy, 8 were included in our final analysis. DATA EXTRACTION: Two authors independently reviewed articles for study results and quality. A third reviewer resolved disagreements. DATA SYNTHESIS: All studies evaluated patients with known tamponade or those referred for pericardiocentesis with known effusion. Five features occur in the majority of patients with tamponade: dyspnea (sensitivity range, 87%-89%), tachycardia (pooled sensitivity, 77%; 95% confidence interval [CI], 69%-85%), pulsus paradoxus (pooled sensitivity, 82%; 95% CI, 72%-92%), elevated jugular venous pressure (pooled sensitivity, 76%; 95% CI, 62%-90%), and cardiomegaly on chest radiograph (pooled sensitivity, 89%; 95% CI, 73%-100%). Based on 1 study, the presence of pulsus paradoxus greater than 10 mm Hg in a patient with a pericardial effusion increases the likelihood of tamponade (likelihood ratio, 3.3; 95% CI, 1.8-6.3), while a pulsus paradoxus of 10 mm Hg or less greatly lowers the likelihood (likelihood ratio, 0.03; 95% CI, 0.01-0.24). CONCLUSIONS: Among patients with cardiac tamponade, a minority will not have dyspnea, tachycardia, elevated jugular venous pressure, or cardiomegaly on chest radiograph. A pulsus paradoxus greater than 10 mm Hg among patients with a pericardial effusion helps distinguish those with cardiac tamponade from those without. Diagnostic certainty of the presence of tamponade requires additional testing.

Antiplatelet agents are central to the treatment and prevention of cardiovascular disease. Although aspirin is the most widely used agent, randomized trials have assessed whether adding clopidogrel to aspirin ("dual-antiplatelet therapy") offers additional benefit with acceptable safety. Unfortunately, these trials have reached conflicting results, in part because of the heterogenous populations they studied. To clarify the role of dual-antiplatelet therapy for patients with vascular disease, a systematic review and meta-analysis of randomized controlled trials was performed. Medline and the Cochrane Collaboration and American College of Physicians Journal Club databases were searched for trials published from 1966 to August 2006 that compared aspirin and clopidogrel with antiplatelet monotherapy. Only trials that presented clinically relevant efficacy and safety outcomes were included. From each trial, demographic data and outcomes were recorded. Summary odds ratios and 95% confidence intervals (CIs) were calculated using a random-effects model. Eight trials comprising 91,744 patients were included. Mean follow-up ranged from 28 days to 18 months. Compared with aspirin alone, dual therapy with aspirin and clopidogrel reduced the odds ratio of the composite outcome of death, reinfarction, and stroke by 15% (95% CI 23% to 6%) in patients with acute coronary syndromes and by 34% (95% CI 44% to 22%) in patients who underwent percutaneous coronary intervention. Dual therapy also significantly reduced the odds of fatal and nonfatal reinfarction in these patient groups but did not significantly reduce the odds of all-cause mortality. Dual therapy was associated with significantly increased risk for major bleeding in studies >1 month in duration (odds ratio 1.80, 95% CI 1.40 to 2.30). In conclusion, combining aspirin and clopidogrel significantly reduces the odds of major cardiovascular events in patients with acute coronary syndromes or those who undergo percutaneous coronary intervention but at the expense of significant increases in the risk for bleeding.

BACKGROUND AND OBJECTIVES: In the general population, an early invasive strategy of routine coronary angiography is superior to a conservative strategy of selective angiography in patients who are admitted with unstable angina or non-ST segment elevation myocardial infarction (MI), but the effectiveness of this strategy in individuals with chronic kidney disease (CKD) is uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a collaborative meta-analysis with data provided by the main authors of identified trials to estimate the effectiveness of early angiography in patients with CKD. The Cochrane, Medline, and EMBASE databases were searched to identify randomized trials that compared invasive and conservative strategies in patients with unstable angina or non-ST MI. Pooled risks ratios were estimated using data from enrolled patients with estimated GFR <60 ml/min per 1.73 m(2). RESULTS: Five randomized trials that enrolled 1453 patients with CKD were included. An early invasive strategy was associated with nonsignificant reductions in all-cause mortality, nonfatal MI, and a composite of death or nonfatal MI. The invasive strategy significantly reduced rehospitalization. CONCLUSIONS: This collaborative study suggests that the benefits of an early invasive strategy are preserved in patients with CKD and that an early invasive approach reduces the risk for rehospitalization and is associated with trends of reduction in the risk for death and nonfatal re-infarction in patients with CKD. Coronary angiography should be considered for patients who have CKD and are admitted with non-ST elevation acute coronary syndromes.

OBJECTIVES: This study is a meta-analysis of prospective cohort studies comparing the impact of cardiac resynchronization therapy (CRT) for patients in atrial fibrillation (AF) and sinus rhythm (SR). BACKGROUND: Although close to one-third of advanced heart failure patients exhibit AF, the impact of CRT in this group remains unclear. METHODS: Prospective cohort studies comparing patients in normal SR and chronic AF treated with CRT were included. All studies reported death, New York Heart Association functional class, ejection fraction, 6-min walk test, and the Minnesota score or its equivalent as outcomes. Data sources included Ovid MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Central Register of Controlled Trials, the Database of Abstracts of Reviews of Effects, and the American College of Physicians Journal Club. RESULTS: Of 2,487 reports identified, 5 studies following a total of 1,164 patients were included. Both AF and SR patients benefited significantly from CRT. Mortality was not significantly different at 1 year (relative risk ratio: 1.57, 95% confidence interval [CI]: 0.87 to 2.81). The New York Heart Association functional class improved similarly for both groups (-0.90 for SR patients, -0.84 for AF patients). SR patients showed greater relative improvement in the 6-min walk test (11.6 m greater, 95% CI: 10.4 to 12.8 m) and the Minnesota score (3.9 points less, 95% CI: 3.4 to 4.5 points) than AF patients. AF patients, however, achieved a small but statistically significant greater change in ejection fraction (0.39% greater change in ejection fraction, 95% CI: 0.22% to 0.55%). CONCLUSIONS: Patients in AF show significant improvement after CRT, with similar or improved ejection fraction as SR patients, but smaller benefits in regard to functional outcomes.

CONTEXT: Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs. OBJECTIVES: To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. DATA SOURCES: Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. STUDY SELECTION: Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. DATA EXTRACTION: We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors' positions on generic substitution as negative, positive, or neutral. RESULTS: We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of beta-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of alpha-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was -0.03 (95% confidence interval, -0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution. CONCLUSIONS: Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.

CONTEXT: Many patients have palpitations and seek advice from general practitioners. Differentiating benign causes from those resulting from clinically significant cardiac arrhythmia can be challenging and the clinical examination may aid in this process. OBJECTIVE: To systematically review the accuracy of historical features, physical examination, and cardiac testing for the diagnosis of cardiac arrhythmia in patients with palpitations. Data Source, Study Selection, and DATA EXTRACTION: MEDLINE (1950 to August 25, 2009) and EMBASE (1947 to August 2009) searches of English-language articles that compared clinical features and diagnostic tests in patients with palpitations with a reference standard for cardiac arrhythmia. Of the 277 studies identified by the search strategy, 7 studies were used for accuracy analysis and 16 studies for diagnostic yield analysis. Two authors independently reviewed articles for study data and quality and a third author resolved disagreements. DATA SYNTHESIS: Most data were obtained from single studies with small sample sizes. A known history of cardiac disease (likelihood ratio [LR], 2.03; 95% confidence interval [CI], 1.33-3.11), having palpitations affected by sleeping (LR, 2.29; 95% CI, 1.33-3.94), or while the patient is at work (LR, 2.17; 95% CI, 1.19-3.96) slightly increase the likelihood of a cardiac arrhythmia. A known history of panic disorder (LR, 0.26; 95% CI, 0.07-1.01) or having palpitations lasting less than 5 minutes (LR, 0.38; 95% CI, 0.22-0.63) makes the diagnosis of cardiac arrhythmia slightly less likely. The presence of a regular rapid-pounding sensation in the neck (LR, 177; 95% CI, 25-1251) or visible neck pulsations (LR, 2.68; 95% CI, 1.25-5.78) in association with palpitations increases the likelihood of a specific type of arrhythmia (atrioventricular nodal reentry tachycardia). The absence of a regular rapid-pounding sensation in the neck makes detecting the same arrhythmia less likely (LR, 0.07; 95% CI, 0.03-0.19). No other features significantly alter the probability of clinically significant arrhythmia. Diagnostic tests for prolonged periods of electrocardiographic monitoring vary in their yield depending on the modality used, duration of monitoring, and occurrence of typical symptoms during monitoring. Loop monitors have the highest diagnostic yield (34%-84%) for identifying an arrhythmia. CONCLUSIONS: While the presence of a regular rapid-pounding sensation in the neck or visible neck pulsations associated with palpitations makes the diagnosis of atrioventricular nodal reentry tachycardia likely, the reviewed studies suggest that the clinical examination is not sufficiently accurate to exclude clinically significant arrhythmias in most patients. Thus, prolonged electrocardiographic monitoring with demonstration of symptom-rhythm correlation is required to make the diagnosis of a cardiac arrhythmia for most patients with recurrent palpitations.

BACKGROUND: Medications for the prevention and treatment of cardiovascular disease save lives but adherence is often inadequate. The optimal role for physicians in improving adherence remains unclear. OBJECTIVE: Using existing evidence, we set the goal of evaluating the physician's role in improving medication adherence. DESIGN: We conducted systematic searches of English-language peer-reviewed publications in MEDLINE and EMBASE from 1966 through 12/31/2008. SUBJECTS AND INTERVENTIONS: We selected randomized controlled trials of interventions to improve adherence to medications used for preventing or treating cardiovascular disease or diabetes. MAIN MEASURES: Articles were classified as either (1) physician "active"-a physician participated in designing or implementing the intervention; (2) physician "passive"-physicians treating intervention group patients received patient adherence information while physicians treating controls did not; or (3) physicians noninvolved. We also identified studies in which healthcare professionals helped deliver the intervention. We did a meta-analysis of the studies involving healthcare professionals to determine aggregate Cohen's D effect sizes (ES). KEY RESULTS: We identified 6,550 articles; 168 were reviewed in full, 82 met inclusion criteria. The majority of all studies (88.9%) showed improved adherence. Physician noninvolved studies were more likely (35.0% of studies) to show a medium or large effect on adherence compared to physician-involved studies (31.3%). Among interventions requiring a healthcare professional, physician-noninvolved interventions were more effective (ES 0.47; 95% CI 0.38-0.56) than physician-involved interventions (ES 0.25; 95% CI 0.21-0.29; p < 0.001). Among physician-involved interventions, physician-passive interventions were marginally more effective (ES 0.29; 95% CI 0.22-0.36) than physician-active interventions (ES 0.23; 95% CI 0.17-0.28; p = 0.2). CONCLUSIONS: Adherence interventions utilizing non-physician healthcare professionals are effective in improving cardiovascular medication adherence, but further study is needed to identify the optimal role for physicians.

BACKGROUND:: Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been advocated as a means to improve procedural outcomes, but the benefit remains unclear. OBJECTIVE:: To synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI. METHODS:: We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation versus PVI alone in patients with paroxysmal and nonparoxysmal AF. RESULTS:: Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (RR 1.15, p=0.03). In the 5 reports of nonparoxsymal AF (3 randomized controlled trials, one controlled clinical trial, and one trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n=112/181 [62%] for PVI+CFAE versus n=84/179 [47%] for PVI alone; RR 1.32, p=0.02). In trials of paroxysmal AF (3 randomized controlled trials and one trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n=131/166 [79%] for PVI+CFAE versus n=122/164 [74%] for PVI alone; RR 1.04, p=0.52). CONCLUSIONS:: In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF.