Autonomic and hemodynamic effects of a new selective dopamine agonist, CHF1035, in patients with chronic heart failure

Dopamine agonists have been studied in chronic heart failure, but earlier reports with non-selective compounds demonstrated unfavourable long-term effects. CHF 1035 is an orally active, new selective dopamine agonist, primarily activating DA(2)- and alpha (2) receptors, thereby inhibiting norepinephrine release, which may be beneficial in heart failure. We conducted a double-blind, placebo-controlled comparison of CHF 1035 (10 mg/day, n = 20) and placebo (n = 9) in patients with mild to moderate chronic heart failure (left ventricular ejection fractio

Long-term follow-up after early intervention with intravenous diltiazem or intravenous nitroglycerin for unstable angina pectoris

Aims In a double-blind randomized trial in unstable angina it was shown that intravenous diltiazem reduced ischaemic events in the first 48 h after inclusion better than intravenous nitroglycerin. The present study was performed to establish the long-term prognosis of the randomized patients, with respect to their initial treatment assignment. Methods and Results One year follow-up data on ischaemic end-points and anti-ischaemic medication were recorded. Results were available for all of the 121 randomized patients. One hundred and sixty-seven primary endpoint events were recorded, of which 54 occurred in the first 48 h and 113 during the follow-up. Survival analysis showed that event-free survival was significantly better in the diltiazem group (45.0%) than in the nitroglycerin group (34.4%), P=0.04. The incidence rate after 48 h and one year for cardiac death are, respectively, 0% and 4.1%. The trend in anti-ischaemic medication was higher in the nitroglycerin group. For beta-blockers, this trend became significant after 12 months (P=0.03). Conclusion These results show that the initial benefit obtained by early treatment with intravenous diltiazem was preserved during the first year after the initial hospitalization, and that, despite the high risk of cardiac events in our population, the overall mortality 12 months after inclusion was low

The Asp(9) Asn mutation in the lipoprotein lipase gene is associated with increased progression of coronary atherosclerosis

Background Many patients suffering from premature coronary artery disease report a family history for such events. A mutation in a particular gene, which confers susceptibility for atherosclerosis, will be found more frequently in individuals suffering from coronary atherosclerosis than in the general population. We have recently reported the identification of an Asp(9) Asn substitution in the lipoprotein lipase (LPL) enzyme. We analyzed the impact of this mutation on the progression of coronary atherosclerosis and the effect of pravastatin in both carriers and noncarriers. Methods and Results All patients were enrolled in the quantitative coronary angiographic clinical trial REGRESS, which studied the impact of pravastatin therapy on coronary atherosclerosis. The Asp(9) Asn mutation was identified in 38 of 819 (4.8%) patients. Carriers of the mutation more often had a positive family history of cardiovascular disease and lower HDL cholesterol levels than noncarriers. In the placebo group, carriers showed more progression of coronary atherosclerosis than noncarriers: mean reduction of the minimum obstruction diameter of -0.25 mm versus -0.12 mm (P=.029) and increase of percentage diameter stenosis of 6.4% versus 1.4% (P=.004). Moreover, the adjusted relative risk for a clinical event for carriers was calculated at 2.16 (95% CI, 1.09 to 4.29; P=.027). Although the lipid-lowering effect of pravastatin was attenuated in carriers, it appeared that these patients showed a response similar to noncarriers in terms of less progression of atherosclerosis and event-free survival. Conclusions This study shows that heterozygosity for a mutation in the LPL gene, which causes only subtle changes in fasting plasma lipids, may promote the progression of coronary atherosclerosis and diminish clinical event-free survival