Bradykinin for the treatment of cardiovascular disease.

Bradykinin is a vasoactive kinin known to be involved in many biologic processes. Levels of bradykinin have been shown to be elevated in a number of cardiac diseases. It is thought that these elevated levels play a protective role in cardiovascular diseases. Preliminary studies have demonstrated that bradykinin may have beneficial effects on a wide spectrum of cardiovascular disorders. Though much study is still required, bradykinin augmentation represents an exciting new target for the treatment of cardiovascular disease.

Cardiovascular considerations in using topical, oral, and intravenous drugs for the treatment of glaucoma and ocular hypertension: focus on beta-adrenergic blockade.

Glaucoma and ocular hypertension are highly prevalent conditions in individuals over the age of 40 and are commonly seen together in patients with cardiovascular disease. Many of the antiglaucoma medications, when systemically absorbed, affect the sympathetic and parasympathetic nervous systems of patients and can cause cardiovascular toxicity. Such adverse effects are frequently associated with the long-term use of potentially toxic agents in elderly people, who are most prone to chronic eye disease. Moreover, patients may not associate their symptoms with the topical eye medications, and consequently may not report adverse drug effects. Drug-drug interactions can also occur when patients are taking medications for both cardiovascular disease and glaucoma. This review focuses on beta-adrenergic blockers as topical antiglaucoma medications and other topical antiglaucoma drugs. The systemic toxicity of these agents is reviewed, along with the possible drug interactions. Brief mention is also made of other antiglaucoma medications used alone and in combination with topical beta-blockers.

Efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for prevention of stroke.

OBJECTIVE: To determine if 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and nonfatal strokes in patients at increased risk of coronary artery disease. DESIGN: Meta-analysis of randomized controlled trials. Clinical trials were identified by a computerized search of MEDLINE (1983 to June 1996), by an assessment of the bibliographies of published studies, meta-analyses and reviews, and by contacting pharmaceutical companies that manufacture statins. Trials were included in the analysis if their patients were randomly allocated to a statin or placebo group, and reported data on stroke events. Thirteen of 28 clinical trials were selected for review. Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, cholesterol measurements, and the number of fatal and nonfatal stroke events in each arm of therapy. Missing data on stroke events were obtained by contacting the investigators of the clinical trials. MAIN RESULTS: Among 19,921 randomized patients, the rate of total stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast, patients who received statins had a 1.67% stroke rate. Using an exact stratified analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% confidence interval [CI] 0.57, 0.86; p =.0005). The pooled OR for nonfatal stroke was 0.64 (95% CI 0.51, 0.79; p =.00001), and the pooled OR for fatal stroke was 1.25 (95% CI 0.71, 2.24; p =.4973). In separate analyses, reductions in total and nonfatal stroke risk were found to be significant only for trials of secondary coronary disease prevention. Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the relative risk for any stroke outcome. CONCLUSIONS: The available evidence clearly shows that HMG-CoA reductase inhibitors reduce the morbidity associated with strokes in patients at increased risk of cardiac events. Data from 13 placebo-controlled trials suggest that on average one stroke is prevented for every 143 patients treated with statins over a 4-year period.

Meta-analysis of the long-term effect of nifedipine for pulmonary hypertension.

BACKGROUND: Pulmonary hypertensive disorders generally result in a progressively worsening course associated with substantial morbidity and mortality. Nifedipine therapy may provide an effective solution to attenuate the disease state. OBJECTIVE: To assess the magnitude and consistency of the effect of nifedipine on reducing pulmonary artery pressure in patients with pulmonary hypertensive disorders. DESIGN: A meta-analysis of 8 trials of nifedipine therapy. METHODS: Clinical trials were identified by a computerized literature search of MEDLINE and by an assessment of bibliographies of retrieved studies. Trials were selected if they measured the change in pulmonary artery pressures in their subjects after weeks to months of therapy. Eight of 25 conducted trials were selected for review. RESULTS: Meta-analysis of 6 homogeneous trials demonstrated a significant decrease in pulmonary artery pressure: -7 mm Hg (95% confidence interval, -3 to -11 mm Hg; P < .01). Heterogeneity of trial results appeared to be due to differences in the severity of initial pulmonary artery pressures and to differences in the dosage of nifedipine rather than the type of disease state. CONCLUSIONS: Meta-analysis of the trials of nifedipine therapy in patients with pulmonary hypertension demonstrated a decrease in pulmonary artery pressure that was associated with an amelioration of clinical symptoms. Because of the paucity of data, however, larger trials are needed to better define its clinical value.

Efficacy of antibiotic prophylaxis for prevention of Lyme disease.

OBJECTIVE: To determine if antibiotic prophylaxis following a dear tick bite is effective in reducing the risk of developing Lyme disease. DESIGN: Meta-analysis of published trials. DATA IDENTIFICATION: Clinical trials were identified by a computerised literature search of MEDLINE and by an assessment of the bibliographies of published studies. STUDY SELECTION: Trials were included in the analysis if their patients were randomly allocated to a treatment or control group, enrolled within 72 hours following an Ixodes tick bite, and had no clinical evidence of Lyme disease at enrollment. Three trials were selected for review after inclusion criteria were applied. DATA EXTRACTION: Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, and number of adverse events in each arm of therapy. RESULTS OF DATA SYNTHESIS: Among the 600 patients with Ixodes tick bites, the rate of infection in the placebo group was 1.4%. In contrast, patients who received antibiotic prophylaxis had a 0% infection rate. The pooled odds ratio, comparing prophylaxis to placebo, was 0.0 (95% confidence interval 0.0, 1.5) (p = .12). CONCLUSIONS: The available evidence to date suggests that the routine use of antibiotic prophylaxis for the prevention of Lyme disease remains uncertain. Meta-analysis of the controlled trials failed to establish definitive treatment efficacy owing to the small sample size of the combined trials and the low rates of infection following a deer tick bite. A larger randomized trial is needed to demonstrate definitively that prophylaxis is more effective than placebo in reducing the risk of early Lyme disease in endemic areas.

Effect of garlic on total serum cholesterol. A meta-analysis.

OBJECTIVE: To assess the size and consistency of garlic's effect on total serum cholesterol in persons with cholesterol levels greater than 5.17 mmol/L (200 mg/dL). DATA SOURCES: Clinical trials were identified by a computerized literature search of MEDLINE and by an assessment of the bibliographies of published studies and reviews. STUDY SELECTION: Trials were selected if they were randomized and placebo-controlled and if at least 75% of their patients had cholesterol levels greater than 5.17 mmol/L (200 mg/dL). Studies were excluded if they did not provide enough data to compute effect size. Five of 28 studies were selected for review. DATA EXTRACTION: Details of study design, patient characteristics, interventions, duration of therapy, and cholesterol measurements were extracted by one author and were verified by another. DATA SYNTHESIS: Study quality was evaluated by multiple reviewers using a closed-ended questionnaire. Patients treated with garlic consistently showed a greater decrease in total cholesterol levels compared with those receiving placebo. Meta-analysis of homogeneous trials estimated a net cholesterol decrease attributable to garlic of 0.59 mmol/L (95% CI, 0.44 to 0.74) (23 mg/dL [CI, 17 to 29]) (P < 0.001). CONCLUSIONS: Meta-analysis of the controlled trials of garlic to reduce hypercholesterolemia showed a significant reduction in total cholesterol levels. The best available evidence suggests that garlic, in an amount approximating one half to one clove per day, decreased total serum cholesterol levels by about 9% in the groups of patients studied.