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- Brunner-La Rocca, Hans-Peter, et al.
(author)
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Which heart failure patients profit from natriuretic peptide guided therapy? A meta-analysis from individual patient data of randomized trials.
- 2015
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 17:12, s. 1252-1261
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Journal article (peer-reviewed)abstract
- AIMS: Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear.METHODS AND RESULTS: To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) ≤45%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P < 0.02). Age (74 ± 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02).CONCLUSION: The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients.
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- Tricoci, Pierluigi, et al.
(author)
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Thrombin-receptor antagonist vorapaxar in acute coronary syndromes
- 2012
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 366:1, s. 20-33
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Journal article (peer-reviewed)abstract
- BACKGROUND:Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.METHODS:In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.RESULTS:Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups.CONCLUSIONS:In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
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