Simon Weber

Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial

BACKGROUNDnCalcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial. We aimed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris.nnnMETHODSnWe randomly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS (gastrointestinal therapeutic system) 60 mg once daily and 3840 to placebo. The primary endpoint was the combination of death, acute myocardial infarction, refractory angina, new overt heart failure, debilitating stroke, and peripheral revascularisation. Mean follow-up was 4.9 years (SD 1.1). Analysis was by intention to treat.nnnFINDINGSn310 patients allocated nifedipine died (1.64 per 100 patient-years) compared with 291 people allocated placebo (1.53 per 100 patient-years; hazard ratio 1.07 [95% CI 0.91-1.25], p=0.41). Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo (0.97 [0.88-1.07], p=0.54). With nifedipine, rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo (0.89 [0.83-0.95], p=0.0012). The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine, despite an increase in peripheral revascularisation. Nifedipine had no effect on the rate of myocardial infarction.nnnINTERPRETATIONnAddition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival. Nifedipine GITS is safe and reduces the need for coronary angiography and interventions.

Combination therapy with tirofiban and enoxaparin in acute coronary syndromes

BACKGROUNDnTirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit.nnnMATERIALS AND METHODSnFifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microgram/kg/min i.v.) for 48-108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) (n=26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) (n=27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban.nnnRESULTSnCoadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7+/-59.8 and 187.5+/-81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients (P=NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P=0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. > or =30 min for tirofiban and unfractionated heparin (P=NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P=0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria.nnnINTERPRETATIONnThe more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.

Combination of copeptin and high-sensitivity cardiac troponin T assay in unstable angina and non-ST-segment elevation myocardial infarction: A pilot study

BACKGROUNDnHigh-sensitivity cardiac troponin assays have improved the detection of acute coronary syndrome.nnnAIMnTo examine the possible incremental value of copeptin in the detection of acute coronary syndrome.nnnMETHODSnWe designed a prospective cohort study to compare the performance of high-sensitivity cardiac troponin T (hs-cTnT) measured at admission in combination with copeptin, and the performance of hs-cTnT alone, measured at admission, 3 hours and 6 hours, in patients with suspected acute coronary syndrome of < 6 hours duration after onset of symptoms (exclusion of patients with ST-segment elevation myocardial infarction).nnnRESULTSnFifty-eight consecutive patients fulfilled our criteria and were included. After detailed investigations, the final adjudicated diagnosis was acute coronary syndrome in 30 patients (including acute myocardial infarction in 13 and unstable angina in 17) and non-acute coronary syndrome in 28 patients. Measured on admission, hs-cTnT concentration was > 14 ng/mL (99 th percentile) in 22 patients with acute coronary syndrome; repetition of the measurement at 3 hours and 6 hours identified three and four additional patients, respectively. The combination of copeptin with hs-cTnT determined on admission identified 26 patients with acute coronary syndrome, with a negative predicted value of 82.6%. The area under the receiver operating characteristic curve was 0.90 for hs-cTnT measured on admission, and 0.94 if repeated at 3 hours and 6 hours or combined with copeptin measurement at admission (non-significant difference).nnnCONCLUSIONSnThis prospective study demonstrated that a dual marker strategy that combines hs-cTnT with copeptin increased slightly the detection of acute coronary syndrome at admission.

N-terminal pro-brain natriuretic peptide in systemic sclerosis: a new cornerstone of cardiovascular assessment?

Background: Cardiac involvement, a common and often fatal complication of systemic sclerosis (SSc), is currently detected by standard echocardiography enhanced by tissue Doppler echocardiography (TDE). Objective: The performance of the biomarker of cardiovascular disease, N-terminal pro-brain natriuretic peptide (NT-proBNP), in the detection of cardiac involvement by SSc was examined. Methods: A total of 69 consecutive patients with SSc (mean (SD) age 56 (13) years, 56 women) were prospectively studied with standard echocardiography and TDE measurements of longitudinal mitral and tricuspid annular velocities. Plasma NT-proBNP was measured in all patients. Results: Overall, 18 patients had manifestations of cardiac involvement, of whom 7 had depressed left ventricular and 8 depressed right ventricular myocardial contractility, and 8 had elevated systolic pulmonary arterial pressure. Patients with reduced contractility had increased mean (SD) NT-proBNP (704 (878) pg/ml versus 118 (112) pg/ml in patients with normal myocardial contractility, p<0.001). Similarly, NT-proBNP was higher in patients with (607 (758) pg/ml) than in patients without (96 (78) pg/ml) manifestations of overall cardiac involvement (p<0.001). Receiver operating characteristic analysis showed NT-proBNP reliably detected depressed myocardial contractility and overall cardiac involvement (area under the curve 0.905 (95% CI 0.814 to 0.996) and 0.935 (95% CI 0.871 to 0.996), respectively). Considering patients with SSc with normal echocardiography and TDE as controls, and using a 125 pg/ml cut-off concentration, sensitivity and specificity were 92% and 71% in the detection of depressed myocardial contractility, and 94% and 78% for overall cardiac involvement. Conclusions: NT-proBNP reliably detected the presence of cardiac involvement and appears to be a very useful marker to risk stratify patients presenting with SSc.

Meta-Analysis of Renin-Angiotensin-Aldosterone Blockade for Heart Failure in Presence of Preserved Left Ventricular Function:

Background: Heart failure (HF) with a preserved left ventricular (LV) ejection fraction (EF) is the leading cause of hospitalization after 65 years of age. Individual randomized trials have not shown benefits conferred by angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARB) in these patients. To overcome this limitation, we performed a meta-analysis of the randomized trials of ACE inhibitors or ARB in patients with HF and preserved LVEF. Methods: Our search identified 4 randomized trials, comprising a total of 8152 patients, that investigated the effects of ACE inhibitors (n = 1), ARB (n = 2), or both treatments (n = 1). Risk ratios (RR) and 95% confidence intervals (CI) were calculated using a fixed-effect estimate method in the randomised trials. Results: Compared with placebo or no treatment, treatment with ACE inhibition or ARB was associated with lower rates of hospitalization for HF (RR 0.90; 95% CI 0.81-0.99, P = .032), though not cardiovascular mortality (RR 1.01; 95% CI 0.90-1.13, P = 0.858). In 3 studies where these endpoints were combined, the 1-year incidence of cardiovascular death or hospitalization for HF was lowered by ACE inhibition or ARB (RR 0.74; 95% CI 0.58-0.94, P = .014). Conclusion: Compared with placebo, ACE inhibition or ARB significantly lowered risks of (a) hospitalization for HF and (b) the combined endpoint of cardiovascular mortality and hospitalization for HF at 1 year, in patients with HF and preserved LVEF. However, they have no significant effect on mortality during more prolonged follow-up; the width of the 95% confidence limits is compatible with a benefit as big as 10% or a hazard as large as 13%.

Continuation of Amiodarone Therapy Despite Type II Amiodarone-Induced Thyrotoxicosis

AbstractBackground: Amiodarone is a powerful antiarrhythmic drug; however, its use may be complicated by thyrotoxicosis. When this occurs, clinicians must balance the continuation of amiodarone for antiarrhythmic purposes, and the discontinuation of treatment in order to prevent aggravation of the thyrotoxicosis. We studied the consequences of continuation or cessation of amiodarone in patients with type II amiodarone-induced thyrotoxicosis.n Methods: Consecutive patients who developed type II amiodarone-induced thyrotoxicosis between September 1997 and September 2000 were studied. Amiodarone was continued in patients with previous ventricular arrhythmia or supraventricular arrhythmia associated with severe haemodynamic changes and was withdrawn in the other patients. In patients with persistent, severe symptomatic thyrotoxicosis, corticosteroids were added to therapy.n Results: Thirteen patients were studied (nine with previous atrial fibrillation/flutter and four with ventricular tachycardia). Amiodarone treatment was continued in ten patients, including eight patients who received corticosteroids, and was temporarily halted in three patients. All patients recovered, with no difference in the duration of thyrotoxicosis between the two groups. Corticosteroid treatment was well tolerated and seemed to hasten the return to a euthyroid state (mean of 3.7 ± 0.7 months vs 6.3 ± 1.7 months). No recurrence of hyperthyroidism occurred during long-term follow-up.n Conclusion: In patients who require amiodarone, treatment may be safely continued despite the development of type II amiodarone-induced thyrotoxicosis.

In-hospital outcomes and long-term mortality according to sex and management strategy in acute myocardial infarction. Insights from the French ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2005 Registry

BACKGROUNDnThe early mortality of acute myocardial infarction (AMI) has dramatically decreased in the recent past. Whether the previously reported sex disparities in use of invasive strategies (IS) persist and translate into differences in outcomes deserves to be examined.nnnMETHODSnWe used the data from a nationwide French prospective multicentre registry from 3,670 AMI patients (1155 women (31.5%), 2515 men (68.5%)) recruited in 223 centres in 2005 and followed-up for 5 years. We examined in-hospital outcomes and 5-year mortality in patients categorized according to sex and use of IS (i.e. coronary angiography during the hospitalisation with a view to revascularisation).nnnRESULTSnIS was less frequently used in women than in men (adjusted OR=0.66; 95% CI: 0.52-0.85), regardless of the type of AMI, age group or risk category, while use of recommended medications was similar at 48 hours and discharge. In-hospital mortality did not differ according to sex, whatever the age group and use of an IS. At 5 years, overall and post-discharge mortality were similar in men and women. However, IS was associated with lower 5-year mortality in women (HR=0.66; 95% CI: 0.51-0.86) as in men (HR=0.48; 95% CI: 0.38-0.60) and there was no sex-strategy interaction.nnnCONCLUSIONSnInvasive strategy remains less frequently used in women than in men, yet is associated with improved five-year survival irrespective of sex. Whether reducing the sex gap in its use would translate into a higher survival in women remains an open question.nnnCLINICAL TRIAL REGISTRATIONnNCT 00673036.

Mid-regional pro atrial natriuretic peptide allows the accurate identification of patients with atrial fibrillation of short time of onset: A pilot study

OBJECTIVESnAtrial fibrillation (AF) is a common arrhythmia; its most prevalent and devastating complication is stroke. A delay of AF onset >48 h is believed to be clinically significant. Mid-regional pro A-type natriuretic peptide (MR-proANP) could be of interest in the identification of the time from onset of AF to presentation.nnnDESIGN AND METHODSnWe measured MR-proANP plasma concentration at presentation in consecutive patients in whom onset of AF was determined, without evidence of concomitant acute heart failure.nnnRESULTSnForty-seven patients were included. Patients with an AF onset <48 h (n=19) had decreased MR-proANP concentrations versus patients with onset >48 h (144.0 [129.2-213.7] versus 321.7 [236.4-425.6] pmol/L, p<0.001); MR-proANP was the only independent variable associated with AF <48 h according to multivariate analysis. Area under the ROC curve for identify AF onset <48 h was 0.878 [95%CI 0.778-0.978].nnnCONCLUSIONSnMR-proANP concentration may reliably identify the time from onset of AF to presentation.

Acute myocardial infarction secondary to platelet apheresis in a 57-year healthy donor

Platelet donation by plateletpheresis is known to induce platelet and coagulation activation but there is no clear relationship between this acquired pre-thrombotic state and acute coronary syndrome in healthy donors. We report an acute myocardial infarction immediately following plateletpheresis in a 57-year-old donor with low atherosclerotic risk profile and no angiographic evidence of atherosclerotic disease strongly suggesting a causal relationship.

Performance of glycogen phosphorylase isoenzyme BB is weak in the detection of patients with non-ST-elevation acute coronary syndrome.

OBJECTIVEnTo examine the diagnostic performance of glycogen-phosphorylase-isoenzyme-BB (GPBB) combined with cardiac troponin I (cTnI) in acute coronary syndrome (ACS).nnnDESIGN AND METHODSnSixty patients with chest pain were investigated; GPBB and cTnI were measured.nnnRESULTSnACS was confirmed in 31 patients; cTnI was >0.07 μg/L in 15 patients and GPBB was >10 μg/L in 6 patients. Areas under ROC curves were similar: 0.854 (cTnI+GPBB) vs. 0.843 (cTnI), p=0.728.nnnCONCLUSIONnCombination of GPBB with cTnI does not improve the detection of ACS.