Fatal sepsis and systemic inflammatory response syndrome after off-label prasugrel: a case report.

Aggressive dual antiplatelet therapy is associated not only with more bleeding, impaired wound healing, and potentially more solid cancer rates but it also causes higher infection risks including sepsis, and systemic inflammatory response syndrome (SIRS). This may be especially true considering the alarming off-label use of prasugrel. A 65-year-old white male patient with a history of myocardial infarction treated with percutaneous coronary intervention and implantation of 2 bare metal stents, was treated with off-label clopidogrel for 4 years, including a double daily dose (150 mg) for the initial 13 months. Still on clopidogrel, the patient was hospitalized with suspected pneumonia. A diagnostic cardiac catheterization revealed a 60%-70% blockage of the mid left anterior descending, but there was no need for coronary intervention. At discharge, clopidogrel 75 mg/d was switched over to off-label prasugrel 10 mg/d on top of aspirin (81 mg/d). On day 3 after prasugrel was given, a football-sized bruise appeared on the patient's lower right abdomen, but computed tomography results were unremarkable. On day 6 after administration of prasugrel, the patient became dizzy, disoriented, confused, experienced difficulty breathing, severe headache, weakness, intensive petechial rash covering the entire body, and breathing difficulty requiring ventilation. Within 24 hours, the patient was unable to correctly identify his age; his eyes were pale in color to almost colorless and when hearing a sound he would turn his entire head toward the sound and he appeared to be blind. His lungs, liver, and kidneys began to show signs of failure over the next 5-9 days. Sixteen days after the administration of the first prasugrel dose, the patient died of sepsis complicated with SIRS. Aggressive off-label use of clopidogrel (double dose for 13 months, and >4 years overall duration), followed by off-label switchover to the highest daily dose (10 mg) prasugrel may trigger sepsis and fatal SIRS. The mechanism responsible for such harmful association is probably indirect, and involves the weakening of platelet-neutrophil-endothelial crosstalk necessary to combat infections, and/or keep inflammation from spreading.

Gastrointestinal adverse events after dual antiplatelet therapy: clopidogrel is safer than ticagrelor, but prasugrel data are lacking or inconclusive.

Current guidelines offer a choice of P2Y12 receptor antagonist among clopidogrel, prasugrel or ticagrelor on top of aspirin (ASA) for dual antiplatelet therapy (DAPT) in patients after acute coronary syndromes (ACS). However, the comparative risks of gastrointestinal (GI) adverse events during DAPT are not clear. Two large ACS trials (TRITON and PLATO) provide a valuable opportunity to directly match the risks of GI complications among current antiplatelet regimens. We compared the rates of GI adverse events after prasugrel and ticagrelor versus clopidogrel based on the Food and Drug Administration (FDA) clinical safety reviews. When compared with ticagrelor, clopidogrel is safer with regard to GI-related risks including fewer overall GI/anal bleeding events and spontaneous GI hemorrhagic episodes, less nausea, vomiting, dyspepsia and diarrhea, and a lower rate of presence of Helicobacter pylori. Among GI symptoms, only constipation was more common after clopidogrel than following ticagrelor. There were extrahepatic risks observed with ticagrelor but not with prasugrel when compared to clopidogrel. Prasugrel unquestionably caused more bleeding from the GI tract and GI malignancies than clopidogrel. However, the entire spectrum of GI effects of prasugrel is much less well known and mostly based on sponsor analysis rather than FDA-verified numbers. Among 3 DAPT options on top of ASA, clopidogrel seems to represent the safest alternative, although comprehensive data on direct prasugrel-associated GI effects are lacking or inconclusive.

Effects of acute hypoxia on left and right ventricular contractility in chronic obstructive pulmonary disease.

The purpose of this investigation was to assess the effects of acute hypoxia on left (LV) and right ventricular (RV) contractility in clinically stable chronic obstructive pulmonary disease (COPD) patients. Eleven male patients (mean age 52.4 +/- 12.6 years) who were diagnosed to have COPD were included into the study. All of the patients underwent left and right heart catheterization. RV contractility was measured according to the method of Ferlinz and LV contractility according to the method of Kennedy and colleagues using indirect digital substraction angiography. Mean pulmonary artery pressures (Mean PPA) and oxygen saturation of the pulmonary artery (SaO2) were measured before and at each stage of graded hypoxic exposure 14%, 12%, and 10% of O2. Right atrial pressures (PRA,syst, PRA,diast, PRA,mean), RV pressures (PRV,syst, PRV,diast, PRV,mean, PRV,end-diast), RV and LV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI), cardiac index (CI), ejection fraction (EF), and heart rate (HR) were calculated before and after breathing a hypoxic mixture of 10% of O2 for 30 minutes. Acute hypoxia induced significant elevation of mean PPA, PRA,syst, PRA,diast, PRA,mean, PRV,syst, PRV,mean, PRV,end-diast, RV EDVI, RV ESVI, LV EDVI, LV ESVI, confidence interval, and HR (p < 0.05). Whereas SaO2 decreased significantly after acute hypoxia (p < 0.05). These findings suggest that the systolic performance of the right and left ventricles were well-maintained during acute hypoxia in patients with COPD.

Current role of laser angioplasty of restenotic coronary stents.

Treatment of in-stent restenosis (ISR) with conventional percutaneous transluminal coronary angioplasty (PTCA) causes significant recurrent neointimal tissue growth in 30-85%. Therefore, laser ablation of intrastent neointimal hyperplasia before balloon dilation can be an attractive alternative. However, the long-term outcomes of such treatment have not been studied thoroughly enough. This prospective case-control study evaluated angiographic and clinical outcomes of PTCA alone and a combination of excimer laser coronary angioplasty (ELCA) and adjunct PTCA in 125 patients with ISR. ELCA was performed before balloon dilation in 67 patients, PTCA alone was performed in 58 patients. Basic demographic and clinical data were comparable in both groups. Lesions included in ELCA group were longer (17.1+/-9.9 vs 13.6+/-9.1 mm; p = 0.034), more complex (36.5% type C stenoses vs 14.3%; p = 0.006), and more frequently had reduced distal blood flow (TIMI <3: 18.9% vs 4.8%; p = 0.025) compared to lesions in the PTCA group. Immediate angiographic results of PTCA and ELCA + PTCA appeared to be comparable. PTCA alone was successful in 57 patients (98.3%), ELCA + PTCA, in 66 patients (98.5%). The rates of hospital complications were comparable (3.0% in ELCA group vs 8.6% in PTCA group). The 1-year follow-up showed that the rates of major adverse cardiac events (MACE) were comparable in the 2 groups (37.3% in ELCA group vs 46.6% in PTCA group). The rates of target vessel revascularization (TVR) within 1 year after the intervention were also similar in the 2 groups (32.8% vs 34.5%). The data mean that ELCA in patients with complex ISR is efficient and safe. Despite a higher complexity of lesions in the ELCA group, no increase in the rate of complications was registered.

Femoral pseudoaneurysm due to diagnostic or interventional angiographic procedures.

The authors investigated the incidence of, diagnostic methods for, and treatment strategies for iatrogenic femoral pseudoaneurysms in their hospital and compared the results with those in the literature. The hospital records of 25,273 patients who had coronary or peripheral angiography and angioplasty in Sani Konukoglu Medical Center from September 1997 to December 2002 were collected retrospectively. All the complications were detected and femoral pseudoaneurysm cases were selected. Diagnostic criteria and treatment strategy were documented. All results were compared with the literature. Femoral pseudoaneurysm was the second in number of complications and bleeding the first. Twenty-eight patients with pseudoaneurysm were diagnosed with color Doppler ultrasound (US) imaging (0.11%). Eleven of these closed spontaneously within 3-7 days. Image-guided compression therapy was applied to the remaining 17 and was effective in 10. The remaining 7 patients were operated on successfully. In this series the incidence of iatrogenic femoral pseudoaneurysm was comparable with the literature (0.02%-2%). Color Doppler US is the best diagnostic tool for this complication, and no other method was necessary. Eleven cases of spontaneous closure may show a rather benign prognosis, but close follow-up is advised. Image-guided compression is also an effective and noninvasive method of therapy for this complication. In late cases with a thick neck, surgery should be done immediately. It is easy to prevent rather than treat this complication. The similar incidence in the literature and in this series shows that a number of complications are to be expected, and so prompt and early diagnosis and effective treatment are very important. Application of good external compression after catheterization, selecting the thinnest introducer, use of B-mode and color Doppler US imaging for suspected cases, and image-guided compression therapy are also effective in early cases with a thin neck of the aneurysm.