Clinical outcomes comparing eptifibatide and abciximab in ST elevation acute myocardial infarction patients undergoing percutaneous coronary interventions.

BACKGROUND: Randomized clinical trials comparing glycoprotein IIb-IIIa inhibitors have largely excluded patients with ST segment elevation myocardial infarction (STEMI). METHODS: We conducted an open-label, sequential comparison of in-hospital and 6-month clinical outcomes in STEMI patients receiving eptifibatide or abciximab as adjunctive therapy during percutaneous coronary intervention (PCI). Registry data were collected and compared for STEMI patients undergoing PCI and receiving eptifibatide or abciximab over a 3.5-year period. Six-month follow-up, using telephone interviews, included major adverse cardiac events and functional status. RESULTS: Baseline characteristics were similar for patients receiving eptifibatide (n = 294) or abciximab (n = 158). No significant differences in hospital clinical outcomes were observed for reinfarction (2 vs. 3% for eptifibatide and abciximab, respectively), repeat revascularization (3 vs. 4%), bleeding complications (8 vs. 12%), congestive heart failure (5 vs. 3%), cerebrovascular accidents (0 vs. 2%), renal failure (2 vs. 3%), and all-cause mortality at discharge (5 vs. 4%). No significant difference was seen between groups in all-cause mortality at 6 months (6.5 vs. 6.4%; hazard ratio 0.976; 95% confidence interval 0.43-2.23; log-rank, p = 0.95). CONCLUSIONS: No significant differences were observed in clinical outcomes between STEMI patients receiving eptifibatide or abciximab in the setting of PCI. Considering the substantially lower cost of eptifibatide, these data suggest that eptifibatide can be substituted for abciximab to lower overall medication costs while maintaining beneficial safety and efficacy effects.

Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors.

OBJECTIVES: A subgroup analysis of the Valsartan Heart Failure Trial (Val-HeFT) was performed to evaluate the effects of the angiotensin II receptor blocker, valsartan, in the patients with chronic heart failure (HF) not receiving angiotensin-converting enzyme (ACE) inhibitors. BACKGROUND: The ACE inhibitors reduce mortality and morbidity in patients with HF. Nonetheless, nearly 20% of potentially eligible patients may not be prescribed ACE inhibitors. RESULTS: Val-HeFT was an international, randomized, double-blinded trial that compared valsartan with placebo when added to the prescribed treatment of patients with HF. The two primary end points of the study were all-cause mortality and the composite of all-cause mortality and morbidity (sudden death with resuscitation, hospital admission for HF, or administration of intravenous inotropic or vasodilator drugs for >or=4 h without hospital admission). Of the 5,010 patients enrolled in the trial, 366 (7.3%) were not treated with ACE inhibitors at baseline. The effects of valsartan on the primary and secondary end points of the study were assessed in this subgroup of patients. RESULTS: Both all-cause mortality and combined mortality and morbidity for patients not treated with ACE inhibitors were significantly reduced in the valsartan treatment group compared with the placebo group (17.3% vs. 27.1%, p = 0.017 and 24.9% vs. 42.5%, p < 0.001, respectively). Consistent with the data on clinical events, patients randomized to valsartan showed improvements in physiologic variables, such as ejection fraction, left ventricular internal diameter in diastole, and plasma neurohormone levels. Permanent discontinuation of study treatment because of adverse experiences was comparable between the two groups. CONCLUSIONS: Val-HeFT has provided the first placebo-controlled outcome data demonstrating a favorable effect of an angiotensin receptor blocker on mortality and morbidity in patients with HF not treated with ACE inhibitors. Based on these results, valsartan appears to be an effective therapy in ACE inhibitor-intolerant patients.

Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study.

OBJECTIVES: The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy. BACKGROUND: The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling. METHODS: At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.4 months. Serial echocardiographic measurements of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility calculated to 90% power at 5% significance defined detectable differences of 0.09 cm for LVIDd and 0.86% for EF. RESULTS: Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 +/- 0.5 versus 3.7 +/- 0.5 (cm/m(2)) and 26.6 +/- 7.3 versus 26.9 +/- 7.0 (%). Mean group changes from baseline over time were compared. Significant decrease in LVIDd and increase in EF began by four months, reached plateau by one year, and persisted to two years in valsartan compared with placebo patients, irrespective of age, gender, race, etiology, NYHA classification, and co-treatment therapy. Changes at 18 months were -0.12 +/- 0.4 versus -0.05 +/- 0.4 (cm/m(2)), p < 0.00001 for LVIDd, and +4.5 +/- 8.9 versus +3.2 +/- 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in EF were no different between valsartan and placebo groups. CONCLUSIONS: The Val-HeFT echocardiographic substudy of 5,010 patients with moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed LV remodeling.

Regional intracoronary analgesia during percutaneous transluminal coronary angioplasty.

The ischemic pain associated with balloon inflation during coronary angioplasty remains a significant source of procedural discomfort and sets a limit on the duration of percutaneous transluminal intravascular interventions. The present study examined whether intracoronary lidocaine reduced the pain of coronary angioplasty. Sixteen patients undergoing elective coronary angioplasty underwent three 90 sec balloon inflations: the first with administration of no intracoronary agent, and the second and third with administration of one or the other of placebo or an equal volume of lidocaine (10-16 mg). Placebo or lidocaine were randomized in administration sequence and were given just before balloon inflation. During the occlusions, pain was scored on an ordinal scale (0 = no pain; 10 = most severe pain). Lidocaine delayed the onset of pain (23 +/- 4 vs. 48 +/- 7 sec, P < 0.005) and reduced its magnitude (at end-inflation: 7.8 +/- 1.3 vs. 3.2 +/- 1.3, P < 0.01). There were no significant hemodynamic or electrophysiologic effects in this group of patients, although atrioventricular conduction was delayed when lidocaine was administered into the epicardial coronary which had the atrioventricular node artery as a branch. Intracoronary analgesia with lidocaine is safe and effective in a select group of patients with normal ventricular function undergoing elective coronary angioplasty.

Effects of valsartan and valeryl 4-hydroxy valsartan on human platelets: a possible additional mechanism for clinical benefits.

Valsartan selectively blocks angiotensin II binding to the AT1 receptor. ince platelet activation plays a key role in the pathogenesis of vascular disease, and because AT1 receptors are present on the platelet surface, we assessed the in vitro effects of valsartan and its metabolite, valeryl 4-hydroxy valsartan (V4HV), on platelets in 30 subjects with multiple risk factors for cardiovascular disease. Platelet characteristics in blood samples pretreated and incubated with 10 nmol to 100 micromol concentrations of valsartan and V4HV were assessed by aggregometry, rapid platelet analyzers, and by flow cytometry. Pretreatment of blood with valsartan and V4HV resulted in inhibition of conventional plasma (ADP, P = 0.0001, valsartan; epinephrine, P = 0.0001, V4HV) and whole blood collagen-induced (P = 0.01, valsartan; P =.0001, V4HV) platelet aggregation. Closure time was delayed (P = 0.02, valsartan; P = 0.03, 4VHV), indicating platelet inhibition in whole blood under high shear conditions. Expression of many surface platelet receptors, namely GP IIb/IIIa antigen, and activity, vitronectin, p-selectin, and LAMP-1 was significantly reduced compared with autologous baseline activity. Intensity of platelet-leukocyte formation and other platelet activation markers remained unchanged. Platelet inhibition was not dose dependent and was more potent for 4VHV than valsartan in the therapeutic range.Valsartan and 4VHV exhibited significant in vitro inhibition of human platelets. Their antiplatelet properties, especially more potent activity of the metabolite appear to be independent of those of other antiplatelet agents. Whether valsartan reduces vascular ischemic events via additional pathways of platelet inhibition in patients with myocardial infarction and ischemic stroke requires further clinical research.