Primary angioplasty versus no reperfusion therapy in patients with acute myocardial infarction and a pre-hospital delay of > 12-24 hours: results from the pooled data of the maximal individual therapy in acute myocardial infarction (MITRA) registry and the myocardial infarction registry (MIR).

OBJECTIVE: In patients with acute myocardial infarction (AMI), treatment with thrombolysis is superior to no reperfusion therapy only up to 12 hours after the onset of symptoms. There are no data addressing whether this time limit is also justified for treatment with primary angioplasty. DESIGN: The pooled data of two German ST-segment elevation AMI registries, the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study and the Myocardial Infarction Registry (MIR), were analyzed. PATIENTS: Out of 22,749 patients, eight hundred and forty-eight with a pre-hospital delay of > 12 hours and < or = 24 hours were treated with either primary angioplasty (94/848; 11.1%) or no reperfusion therapy (754/848; 88.9%). RESULTS: Patients treated with primary angioplasty were 10 years younger (59 years versus 69 years; p = 0.001), more often male [72.3% versus 59.9%; odds ratio (OR) = 0.57; 95% confidence interval (CI) = 0.36-0.92] and less likely to be diabetics (17% versus 27.2%; OR = 0.55; 95% CI = 0.31-0.97). Hospital mortality was 8.5% in patients treated with primary angioplasty compared to 17.1% in patients with no reperfusion therapy (OR = 0.45; 95% CI = 0.21-0.95; p = 0.033) and the combined endpoint (death, reinfarction or stroke) occurred significantly less often (11.7% versus 20.3%; OR = 0.52; 95% CI =0.27-1; p = 0.045). However, multiple logistic regression showed only a non-significant trend for lower mortality (OR = 0.54; 95% CI =0.20-1.23) and the combined endpoint (OR = 0.65; 95% CI = 0.29-1.31) in patients treated with primary angioplasty. CONCLUSIONS: These data show the possibility of a benefit of primary angioplasty over conservative treatment in patients with pre-hospital delays of > 12 up to 24 hours, although multiple logistic regression analysis failed to find significant differences between treatments. This might be due to inadequate study power or a selection bias. These findings encourage further investigation of this subject.

Acute and long-term hemodynamic effects of pimobendan (UD-CG 115 BS) in comparison with captopril.

The acute and long-term hemodynamic efficacy of the positive inotropic and vasodilatory drug pimobendan (5 mg b.i.d.) was compared with that of the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg t.i.d.) in a double-blind, randomized study in 20 patients suffering from chronic congestive heart failure (NYHA functional classes II-III). The hemodynamics at rest and under comparable exercise conditions were always obtained on the first and 14th treatment day before and 2 h following drug administration. Under resting conditions, pimobendan reduced the end-diastolic pulmonary arterial pressure measured 2 h after drug administration by 33% (p less than 0.05) and increased the cardiac output by 16% (p less than 0.05). These effects were maintained after a treatment period of 14 days. Following administration of captopril, no significant hemodynamic changes at rest were noted 2 h after the first dose on day 1 and the last dose on day 14. There was, however, a tendency to continuous decline of the end-diastolic pulmonary arterial pressure over the study period. Under comparable work load (median of 25 W), both substances decreased the end-diastolic pulmonary arterial pressure 2 h following the first dose (pimobendan, -38%, p less than 0.01; captopril, -9%, p less than 0.05). The difference in the magnitude of effect between both treatment groups was statistically significant (p less than 0.01). Following a treatment period of 14 days, the end-diastolic pulmonary arterial pressure before drug administration was significantly reduced (-24%, p less than 0.05) only in the pimobendan group, whereas the reduction in the captopril group (-11%) could not be statistically verified.(ABSTRACT TRUNCATED AT 250 WORDS)

Performance of Bayesian feedback to forecast lidocaine serum concentration: evaluation of the prediction error and the prediction interval.

The prediction performance of the Bayesian feedback method was evaluated with respect to accuracy and precision, and efficacy and safety (width of the prediction interval) on the basis of 90 predictions in 30 patients treated with lidocaine. The mean of the prediction error (PE) and the root mean squared error (RMSE) served as a measure of accuracy and precision. The variance of the standardized prediction error (SPE) was used to evaluate the estimate of the standard deviation of the prediction error. SPE was defined as PE divided by the standard deviation of the predicted concentration. The standard error of RMSE and of the variance of SPE was determined by bootstrap. The results indicate that the lidocaine serum concentration at 12 hr (C2) after starting continuous infusion can be predicted with high accuracy and precision with a single feedback measurement obtained 2-4 hr (C1) after commencement of treatment: RMSE = 20.6%. Prediction at 24 hr (C3) was less accurate: RMSE = 31.4%. Using both C1 and C2 to predict C3 improved precision (RMSE = 23.4%). The evaluation of the prediction interval revealed that the current algorithm produces an upward biased estimate, probably due to a positive bias in the estimate of the covariance matrix of the parameter estimates. It is suggested that evaluation of prediction performance should include the estimate of the prediction interval.

[Treatment of congestive cardiac failure with vasodilators (author's transl)]. / Behandlung der Stauungsherzinsuffizienz mit Vasodilatatoren. Vergleich der Akut- und Langzeiteffekte unter Berücksichtigung verschiedener Substanzgruppen.

The possibility of development of tolerance of treatment with vasodilators was investigated in 16 patients with severe chronic congestive cardiac failure. Independent of the primary site of action, the first application of a vasodilator resulted in lowering of pulmonary artery pressure by about 30% (isosorbide dinitrate 40 mg orally in delay-action form and 5 mg sublingually, prazosin 2 mg, dihydralazine 75 mg). Only dihydralazine reduced systemic resistance acutely by 42% and increased cardiac minute volume by 66%. After treatment for 12 days with isosorbide dinitrate delay-action (three times 20 mg), prazosin (three times 2 mg) or dihydralazine (three times 75 mg), there was persistent lowering of the pulmonary artery pressure 16 hours after cessation of treatment only after isosorbide dinitrate (-29%) and dihydralazine (-27%). A decrease of systemic resistance by 11% and an increase of cardiac minute volume by 20% were seen only after dihydralazine. An additional acute application of isosorbide dinitrate or dihydralazine resulted in a further decrease of pulmonary artery pressure (-25% and -11%, respectively). An additional decrease of systemic resistance (-23%) and increase of cardiac minute volume (+18%) were again only seen with dihydralazine. In contrast to the first medication there was no significant change of the pulmonary artery pressure after treatment with prazosin for 12 days.

The acute effect of a new positive inotropic agent (AR-L 115 BS) on cardiac hemodynamics and contractility in patients with severe chronic congestive heart failure.

The hemodynamic effect of 2-[(2-methoxy-4-methylsulfinyl)phenyl]- 1H-imidazo[4,5-b]pyridine (AR-L 115 BS), a new positive-inotropic substance, was studied in 10 Patients with chronic congestive heart failure after i.v. infusion of increasing does of 1.8 mg/min, 2.7 mg/min and 3.6 mg/min over a period of 40 min each. Prior to each infusion an i.v. bolus of 16 mg was given. The hemodynamic changes were measured by means of a Swan Ganz balloon tipped catheter and by echocardiography. The heart rate remained unchanged whereas systolic, diastolic and mean arterial pressures fell slightly by about 5%. The mean and diastolic pulmonary pressures decreased by 30% with a concomitant increase in cardiac output of 15%. The total peripheral and pulmonary resistance was reduced by 20% and 40%, respectively. The echocardiographically measured fraction of systolic fiber shortening of the left ventricle was increased by 15%. In parallel the ratio of PEP/LVET decreased by 10%. While the increase of the infusion dose from 1.8 mg/min to 2.7 mg/min was followed by an increase in the hemodynamic changes, no further alterations were observed after the dose was increased from 2.7 mg/min to 3.6 mg/min despite a marked increase in the blood level of AR-L 115 BS. The effect was still present 75 min after the infusion had been stopped. The blood level at that time had returned to the level achieved with the dose of 2.7 mg/min. The results are consistent with findings in animals which have shown that AR-L 115 BS exerts not only a positive-inotropic action on the heart, but also exhibits a vasodilating effect, predominantly in the capacitance vessels. As the substance can also be administered orally it could prove to be a useful agent in the management of severe cases of heart failure.