Further information: The Medical Management of Heart Failure (see p1397) from Cardiovascular Medicine, 3rd Edn*

The authors of this meta-analysis [1] examined 23 heart failure trials to evaluate which factor accounted for the effectiveness of treatment in heart failure β-blocker trials, i.e. β-blocker dose or degree of heart rate reduction. Of the 548 trials examined by the authors, 23 randomized, placebo-controlled heart failure trials that also reported all-cause mortality were selected.

Analyses of trials resulted in data showing that β-blockers reduce the risk for death in heart failure patients by 25%. For every heart rate reduction of 5 beats per minute with β-blocker treatment, there was an 18% reduction in the risk of death (confidence interval [CI], 6%–29%). There was no indication of significant relationship between all-cause mortality and β-blocker dosing (risk ratio [RR] for death, 0.74 [CI, 0.64–0.86]) in high-dose β-blocker trials vs. 0.78 [CI, 0.63–0.96] in low-dose β-blocker trials; P for meta-regression=0.69). The authors of this study concluded that while there is a statistically significant survival benefit associated with β-blocker use, the dose is not statistically significant.

[1] McAlister FA, Wiebe N, Ezekowitz JA, et al. Meta-analysis: β-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med 2009;150:784-794

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Coronary Risk Factors: An Overview (see p2609) from Cardiovascular Medicine, 3rd Edn*

Data collected in The Framingham Heart Study [1] that began in 1948 with an original cohort of 5209 patients culminated in the identification of specific common risk factors that contributed to the development of cardiovascular disease (CVD) in patients who had never suffered a heart attract or had experienced symptoms. Algorithms were constructed of standard risk factors (male sex, age, systolic blood pressure, antihypertensive treatment, cholesterol levels, smoking, and diabetes) for risk assessment over a ≤10-year period for doctors to use in a primary care setting. Authors of the current study [2] believe that in order to understand today’s public health burden of CVD, the longer-term risk factors of CVD must be evaluated. Using data collected from the Offspring of the Framingham Heart Study [3], 2333 women and 2173 men (free of CVD and cancer at enrollment) were followed for possible development of “hard” CV events that included coronary death, myocardial infarction, or stroke. Although the results of this study found that the standard risk factors currently in use were still effective in predicting CVD risk over a 30-year follow-up period, the same was not true for the impact of body mass index (BMI) over a 30-year follow-up period. The authors developed a longer-term algorithm that quantified a 30-year risk as a direct function of risk factors that applied to younger individuals and women, accounted for the competing cause of non-CVD mortality, and could be used by the patient’s primary care doctor.

[1] Dawber TR, Meadors GF, Moore FE Jr. Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health 1951; 41:279-286.

[2] Pencina MJ, D’Agostino RB, Larson MG, et al. Predicting the 30-year risk of cardiovascular disease. The Framingham Heart Study. Circulation 2009;109:3078-3084

[3] Kannel WB, Feinleib M, McNamara PM, et al. An investigation of coronary heart disease in families: the Framingham Offspring Study. Am J Epidemiol 1979;110:281-290.

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Coronary Artery Bypass Surgery and Percutaneous Coronary Revascularization: Impact on Morbidity and Moratality in Patients with Coronary Artery Disease (see p1073) from Cardiovascular Medicine, 3rd Edn*

The authors of this study [1] conducted a single-center pilot trial to address not only the long-term use of clopidogrel treatment on platelet function, but also the anti-inflammation effect of the therapy on patients having elective percutaneous coronary intervention (PCI).

The study was comprised of 110 consecutive patients. Sixty-nine patients were clopidogrel-naïve and 41 had been receiving long-term clopidogrel therapy for more than 6 months. While clopidogrel is a medication that has long been used for platelet inhibition, the authors hypothesized that in addition, decreased inflammation would be found in the 41 patients who had received the clopidogrel therapy when compared with the 69 clopidogrel-naïve patients. The study was designed to provide mechanistic support for the inhibition of platelet function by clopidogrel as observed in earlier large-scale clinical trials.

The results of the study showed that clopidogrel diminished platelet aggregation induced by adenosine diphosphate and decreased P-selectin and activated glycoprotein IIb/IIIa expression. This suggests that long-term clopidogrel therapy diminishes platelet aggregation and formation.

[1] Antonio MJ, Mahla E, Bliden KP, et al. Effect of long-term clopidogrel treatment on platelet function and inflammation in patients undergoing coronary arterial stenting. Am J Cardiol 2009;103:1546-1550

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Coronary Artery Bypass Surgery and Percutaneous Coronary Revascularization: Impact on Morbidity and Moratality in Patients with Coronary Artery Disease (see p1073) from Cardiovascular Medicine, 3rd Edn*

The BARI 2D study [1] evaluated treatment strategies for patients with type 2 diabetes who had coronary artery disease. Two treatment strategies were used. They included 1) either prompt revascularization (neither PCI nor CABG was specified, but left to the discretion of the physician prior to randomization) or optimal medical therapy alone, and 2) either insulin-sensitization therapy or insulin-provision therapy that would achieve a target glycated hemoglobin level of less than 7.0%. Primary end-point was death from any cause, and the secondary end-points were a composite of death, myocardial infarction (MI), or stroke.

Although among the treatment strategies, there were no significant differences in the primary end-point or the secondary end-points, the design of the trial allowed comparisons between strategies. For patients who received CABG revascularization, there were lower rates of cardiovascular events than in the medical treatment group. However, as with the original BARI trial, published in The New England Journal of Medicine in 1996 [2], a study that was designed to compare CABG and PCI in patients with multivessel disease, the results left many concerns and questions undecided.

Major advances have been developed in each of the treatment options, i.e. CABG, PCI, and medical therapy, and the constant supply of new data have rendered long-term recommendations difficult to achieve. However, the conclusion of this most recent BARI 2D trial is that there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between therapies strategies of insulin sensitization and insulation provision.

[1] Frye RL, August P, Brooks MM, et al, the BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med 2009;360:2503-2515

[2] The BARI Investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med 1996;335:217-225

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Stem Cell Therapy for Cardiac Disease (see p2754) from Cardiovascular Medicine, 3rd Edn*

The BALANCE Study provides the first 5-year data available on autologous bone-marrow cell (BMC) therapy in patients with acute myocardial infarction (AMI) [1] . It has been termed a “milestone paper” because it reports results of the first long-term BMC transplantation after AMI, and the results showed significant clinical benefit.

A major cause of infarct-related heart failure and death following AMI is ventricular remodeling. The remodeling of the myocardium can be treated medically or by revascularization to improve ventricular function, but not to restore damaged tissue. To evaluate the amount of improvement achieved by BMC therapy, 124 patients with AMI were enrolled into the study, and 62 patients received autologous BMC infused directly into the infarct-related artery 7±2 days post AMI. The control group consisted of 62 patients. Within three months, the therapy group showed significant improvement in ejection fraction (EF), the infarct size was reduced by 8%, and there was improvement in contractility in the infarct zone. In addition, exercise capacity was increased in the treated group, and mortality was significantly reduced.

[1] Yousef M, Schannwell CM, Kostering M, et al. The BALANCE study: Clinical benefit and long-term outcome after intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction. J Am Coll Cardiol 2009; 53:2262-2269.

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Endocrine Disorders and the Heart (see p2295) from Cardiovascular Medicine, 3rd Edn*

Rosiglitazone was evaluated in the RECORD trial [1] when added to the medication regime of patients using metformin, a sulfonylurea, or both to lower blood glucose in patients with type 2 diabetes. The use of the thiazolidinedione rosiglitazone has been the subject of clinical trials in the past, and the results of the RECORD trial still leave unresolved concerns regarding the safety of the drug.

RECORD was a randomized, open-label, dual-therapy trial conducted at 364 centers in Europe and Australia. A total of 4447 patients were enrolled and were randomly assigned to receive rosiglitazone in combination with either metformin or sulfonylurea (n=2220) or a metformin/sulfonylurea combination (n=2227). The primary endpoint was cardiovascular hospitalization or cardiovascular death, and the hazard ratio non-inferiority margin was 1 to 20.

Rosiglitazone is known to cause fluid retention and possibly heart failure, and in the trial, heart failure resulting in admission to the hospital occurred in 61 patients in the rosiglitazone group and 29 in the metformin/sulfonylurea group, thus further supporting the concern. Limb fracture in women increased as well.

The trial did not produce evidence of the drug’s effect on myocardial infarction, and the investigators concluded that the drug does not increase the risk of overall cardiovascular morbidity or mortality. Therefore, the clinical implications for use of rosiglitazone indicated that it should not be used in heart failure patients and should be used with caution in women at risk of fractures, but it is highly effective in glycemic control for patients with type 2 diabetes when used with care.

[1] Home PD, Pocock SJ, Beck-Nielsen H, et al, Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type-2 diabetes. Lancet 2009;373:2125-35

Note: You may need subscriptions to access content from links on this page. You are responsible for obtaining these subscriptions.

* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.