Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study.

BACKGROUND: In trials of patients with left ventricular dysfunction or heart failure, ACE inhibitor use was unexpectedly associated with reduced myocardial infarction (MI). Using the Heart Outcomes Prevention Evaluation (HOPE) trial data, we tested prospectively whether ramipril, an ACE inhibitor, could reduce coronary events and revascularization procedures among patients with normal left ventricular function. METHODS AND RESULTS: In the HOPE trial, 9297 high-risk men and women, >/=55 years of age with previous cardiovascular disease or diabetes plus 1 risk factor, were randomly assigned to ramipril (up to 10 mg/d), vitamin E (400 IU/d), their combination, or matching placebos. During the mean follow-up of 4.5 years, there were 482 (10.4%) patients with clinical MI and unexpected cardiovascular death in the ramipril group compared with 604 (12.9%) in the placebo group [relative risk reduction (RRR), 21% (95% CI) (11,30); P<0.0003]. Ramipril was associated with a trend toward less fatal MI and unexpected death [4.0% versus 4.7%; RRR, 16% (-3, 31)] and with a significant reduction in nonfatal MI [5.6% versus 7.2%; RRR, 23% (9,34)]. Risk reductions in MI were documented in participants taking or not taking beta-blockers, lipid lowering, and/or antiplatelet agents. Although ramipril had no impact on hospitalizations for unstable angina [11.9% versus 12.2%; RRR, 3% (-9,14)], it reduced the risk of worsening and new angina [27.2% versus 30.0%; RRR, 12% (5,18); P<0.0014] and coronary revascularizations [12.5% versus 14.8%; RRR, 18%; (8,26) P<0.0005]. CONCLUSIONS: In this high-risk cohort, ramipril reduced the risk of MI, worsening and new angina, and the occurrence of coronary revascularizations.

Upstream use of tirofiban in patients admitted for an acute coronary syndrome in hospitals with or without facilities for invasive management. PRISM-PLUS Investigators.

Management and prognosis of acute coronary syndromes may be influenced by the availability of catheterization facilities at admitting hospitals. Treatment effects of tirofiban were examined in a Canadian cohort of 834 patients enrolled in the Canadian Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial according to admission into hospitals without (n = 322) or with catheterization facilities (n = 512). Hospital transfers for cardiac catheterization were facilitated using preexisting networks accelerated for the purposes of the protocol. In hospitals without facilities, the relative risks for occurrence of death, infarction, or refractory ischemia among patients receiving tirofiban plus heparin compared with heparin alone were 0.52 at 7 days (p = 0.02), 0.59 at 30 days (p = 0.03), and 0.70 at 180 days (p = 0.09); and for death or infarction, 0.32 (p = 0.02), 0.46 (p = 0.04,) and 0.51 (p = 0.03), respectively. Benefit was seen regardless of transfer status, with no statistically significant interaction between treatment, hospital type, and catheterization for any end point at any time point. The incidence of Thrombolysis In Infarction defined major bleeding with respect to therapy was not significantly different between hospital types. Thus, upstream treatment with tirofiban plus heparin confers clinical benefits in unstable angina and/or non-ST-segment elevation infarction patients regardless of whether initial presentation is to a hospital without catheterization facilities or to a hospital with such facilities.

Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study.

BACKGROUND: Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina. METHODS AND RESULTS: In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 micrograms/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (P = .04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses (P = .03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of > 80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban. CONCLUSIONS: The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.

Preoperative and operative predictive variables of late clinical events following saphenous vein coronary artery bypass graft surgery.

Prediction of late clinical events was studied in a series of 145 patients who had control angiographic studies at one year and between two and 14 years after saphenous vein coronary artery bypass graft surgery. During a mean observation interval of 7.4 years, new narrowing or occlusion occurred in grafts of 59% of the patients and progression in non-bypassed arteries was observed in 66%. One or several of the following events were observed in 56% of the patients: recurrent or worse effort angina, unstable angina, myocardial infarction and heart failure. Unstable angina during follow-up was more frequent in young patients and in those who had this clinical presentation before surgery. The incidence of myocardial infarction was likewise greater in patients who had preoperative unstable angina and in those with four to five risk factors for coronary artery disease, as well as those having a lesser number of inserted grafts. Heart failure was predicted independently by either four to five risk factors, a low left ventricular contraction score or fewer grafts placed at surgery. The number of inserted grafts correlated inversely with any one of the late clinical events.

Atrial natriuretic factor: a possible link between left atrium, plasma volume, adrenergic control and renin-aldosterone in the mitral valve prolapse syndrome.

The immunoreactive atrial natriuretic factor (ANF) was measured by radioimmunoassay after extraction with SEP-PAK cartridges in 16 hyperadrenergic patients with the mitral valve prolapse (MVP) syndrome. Plasma renin activity and plasma aldosterone were concomitantly measured by radio-immunoassay. Plasma and blood volumes were obtained indirectly after measurement of red cell volume. Norepinephrine and epinephrine were measured by a radio-enzymatic microtechnique. Seven out of 16 patients (44%) had high values of immunoreactive ANF. Blood volume was uniformly decreased in MVP patients, but this was more marked in patients with high ANF. There was a significant correlation between ANF and the reduction in blood volume. Plasma norepinephrine was not significantly different in patients with high ANF and low or normal ANF. Thus, some patients with the MVP syndrome may have both an increased adrenergic state and abnormal values of ANF. The interplay between these two neuro-endocrine disorders may account for some of the symptoms of these patients. The data confirm that this syndrome may be associated with a complex 'neuro-endocrine cardiovascular process'.

[Experimental induction of sino-auricular blocks on isolated atria. Microelectrode study of the effects of bepridil]. / Induction expérimentale de blocs sino-auriculaires sur oreillette isolée. Etude par microélectrodes des effets du bépridil.

The effects of bepridil on sinoatrial conduction were studied by perfusing 15 isolate rabbit right atrial preparations. In a preliminary series an increase in cycle length was observed with a dose-dependent effect with concentrations of between 5 X 10(-7) M and 1 X 10(-5) M. At the latter dose, sinoatrial block was observed. Bepridil was therefore used in a series of 10 preparations to induce sinoatrial block (SAB). After 10 minutes perfusion the cycle length increased significantly (14.3%, p less than 0.02). In 4 preparations SAB occurred 18.7 +/- 2.5 minutes after the onset of the perfusion. Sinoatrial block did not occur in 6 cases and in 4 cases an intrasinus shift of the dominant pacemaker was observed. The types of SAB observed were varied and their mechanisms were complex. Different types of SAB occurred in the same preparation. The different types of block recorded were: Blumberger type I SAB, anterograde 2/1 SAB, intrasinus 2/1 block, retrograde 2/1 and advanced block, complete atrio-sinusal dissociation.

Intracellular and extracellular recordings of sinus node activity: comparison with estimated sinoatrial conduction times during pacemaker shifts in rabbit heart.

Sinoatrial conduction times, estimated by premature atrial stimulation, were compared with direct measurement of the sinoatrial conduction time in 15 isolated rabbit sinus node preparations before and after intrasinusal pacemaker shifts induced by cooling. Transmembrane potentials and surface electrograms were recorded from the sinus node and crista terminalis. Extracellular sinus node activity was recorded in five preparations. Mapping was performed at 38 degrees C and 35 degrees C to determine the site of the dominant pacemaker. The sinus cycle was significantly longer at 35 degrees C (319.4 ms vs 258.1 ms). Intracellular measured conduction time was significantly shorter (63.8 ms vs 70.4 ms) because of caudal shift of the dominant pacemaker. Estimated sinoatrial conduction time was significantly longer (110.3 ms vs 85.4 ms) owing to the depression of automaticity by the extrastimulus. Extracellular measured conduction time did not differ significantly from intracellular measured conduction time. These results suggest that intrasinusal pacemaker shift may explain inaccuracies in indirect estimations of sinoatrial conduction time by atrial pacing techniques. Extracellular recordings appear to be a better method of evaluating sinoatrial conduction times.

Risk of preangioplasty occlusion and myocardial infarction in one-vessel-disease patients scheduled for percutaneous transluminal coronary angioplasty.

Coronary occlusion or myocardial infarction occurred in 50 of 394 (13%) one-vessel-disease patients awaiting percutaneous transluminal coronary angioplasty (PTCA). To identify risk factors for these events, we first matched the 37 patients who demonstrated occlusion on the immediate preangioplasty repeat angiogram with 37 patients who did not. Matching was based on the time interval between angiograms, the date of the procedure, and the site of the lesion. Preangioplasty occlusion patients did differ from controls by age (47 +/- 11 vs 54 +/- 8 years, P less than .01), smoking status (34/37 vs 24/37, P less than .01), and angina class (2.6 +/- 1.0 vs 2.3 +/- 0.7, P less than .10) at the time of the first angiogram. Second, we pooled the data of the 37 preangioplasty occlusion patients with those of the 13 patients with preangioplasty myocardial infarction. The 50 cases with complication (coronary occlusion or myocardial infarction) were younger (47 +/- 12 vs 54 +/- 8 years, P less than .01), more often smokers (42/50 vs 24/37, P less than .05), and more symptomatic (2.7 +/- 0.8 vs 2.3 +/- 0.7, P less than .05) than the 37 controls. This study suggests that young smokers with severe angina are at high risk of preangioplasty occlusion and/or myocardial infarction; prompt management of these patients, when considered for PTCA, seems advisable.