Background— Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. Methods and Results— In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups ( P =0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo ( P =0.061 for intent-to-treat population). The primary reason for not completing treatment was ≥1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P <0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76±0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78±0.76 to 80 mm, P =0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm 3 , respectively; P =0.16 to 0.72). Conclusions— Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae.
Journal Article Hypercoagulable state and thromboembolism following warfarin withdrawal in post-myocardial-infarction patients Get access L. GRIP, L. GRIP *From the Departments of Cardiology, Karolinska HospitalStockholm, Sweden Correspondence: Lars Grip, MD, Department of Cardiology, Thoracic Clinics, Karolinska Hospital, S. 10401 Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar M. BLOMBÄCK, M. BLOMBÄCK †Internal Medicine Karolinska HospitalStockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar S. SCHULMAN S. SCHULMAN ‡Clinical Chemistry and Blood Coagulation, Karolinska HospitalStockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, Volume 12, Issue 11, November 1991, Pages 1225–1233, https://doi.org/10.1093/eurheartj/12.11.1225 Published: 01 November 1991 Article history Revision received: 14 June 1990 Received: 05 November 1990 Published: 01 November 1991
To characterize the antithrombotic activity of inogatran per se in a porcine model of copper-coil-induced coronary artery thrombosis and to compare its effect with that of heparin and ASA.Forty-eight pigs were assigned to one of the following groups: (1) saline; (2) heparin, (a) 75 and (b) 150 IU/kg/h; (3) acetylsalicylic acid (ASA), 12.5 mg/kg; (4) ASA 12.5 mg/kg + inogatran, 0.06 mg/kg/h; (5) ASA 12.5 mg/kg + inogatran, 0.30 mg/kg/h; (6) inogatran, 0.30 mg/kg/h; (7) inogatran, 0.60 mg/kg/h; (8) inogatran, 1.5 mg/kg/h. Computerized vectorcardiography was applied to monitor coronary occlusion and reperfusion.Cumulative time in which coronary arteries were patent, expressed as a percentage of the treatment time (i.e., 90 min) in heparin- and ASA-treated pigs, was 8 +/- 6 and 14 +/- 7%, respectively. This is not significantly different from placebo-treated pigs. Inogatran-treated pigs showed a dose-dependent antithrombotic effect, and the average patency rates were 34 +/- 39, 54 +/- 37 and 80 +/- 32%, in groups 6, 7 and 8, respectively. Combined treatment with inogatran and ASA did not significantly improve the antithrombotic effect. A partial antithrombotic effect of inogatran was maintained for, on average, at least 150 min after the end of treatment, as evidenced by patency rates of 31 +/- 43, 52 +/- 48 and 62% +/- 44, in groups 6, 7, and 8, respectively.Inogatran inhibits the formation of arterial thrombosis more effectively than heparin or ASA. Inhibition of clot-bound thrombin and thrombin-induced platelet activation may be the mechanisms behind this effect. Our findings also suggest that a thrombus formed in the presence of inogatran is more susceptible to spontaneous endogenous fibrinolysis.
Current experience from coronary angiographic trials using different treatment regimens such as lifestyle changes, resins, nicotinic acid and statins, shows that progression of atheroma can be retarded, and that regression can sometimes be induced, by a marked lowering of LDL-cholesterol. Young post-myocardial infarction patients, however, usually exhibit a multiplicity of metabolic risk factors with dyslipidaemias, predominantly hypertriglyceridaemia, and disturbances of glucose-insulin homeostasis and of the haemostatic system. These factors, together coupled with coronary angiographic data showing that the degree of dyslipidaemia is related to the extent and degree of coronary atherosclerosis, and the fact that rapid progression of coronary atherosclerosis was foreseen in this group of patients, resulted in the initiation of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) in 1985. BECAIT was a 5-year, double-blind, placebo-controlled study of bezafibrate (200 mg three times daily) and dietary intervention in dyslipidaemic male survivors of myocardial infarction below 45 years of age. The angiographic analysis included 81 patients (42 bezafibrate and 39 placebo) who underwent baseline and at least one post-treatment angiogram, at 2 and 5 years. Changes in mean minimum lumen diameter indicated that there was 0·13 mm less (95% CI: 0·10; 0·15) disease progression in focal lesions in the bezafibrate group than in the placebo group (P=0·049). Parallel, but non-statistically significant, treatment effects were observed for mean segment diameter and percent stenosis. Three patients treated with bezafibrate and 11 patients in the placebo group suffered coronary events during the course of the trial (P002 logrank test). The angiographic effects of bezafibrate were accompanied by statistically significant reductions in serum cholesterol and triglycerides. Furthermore, plasma fibrinogen levels were significantly reduced and HDL-cholesterol concentration increased but there was no net change in LDL-cholesterol. These findings show that bezafibrate slowed the progression of focal coronary atherosclerosis to a degree that is comparable to that achieved with the statins in angiographic trials such as MAAS and REGRESS. Bezafibrate also reduced the occurrence of coronary events in young post-infarction victims. Like BECAIT, analyses of data from the NHLBI type II study, CLAS, POSCH and MARS provide evidence for the role of triglyceride-rich lipoproteins in the progression of coronary artery disease. Retardation of progression of atherosclerosis and a reduction in coronary events is, therefore, possible without reducing LDL-cholesterol.
Modern care is often based on investigations such as laboratory markers and imaging -for example, X-ray or ultrasound.The results contribute to a diagnosis and, if judged necessary, treatment is initiated.This diseased-oriented approach is the prevailing mode of management in modern medicine.In contrast, person-centered care (PCC) takes the point of departure from each person´s subjective experience of illness and its impact on daily life.A patient is considered as a person with emotions and feelings.PCC is considered present within clinical care according to a definition articulated by the Centre for Person Centred Care at the University of Gothenburg (GPCC) when three core components are present: elicitation of a detailed patient narrative; formulated partnership between caregiver and patient and documentation of the partnership in the patient record.Accordingly, when there is an illness requiring care and the person is attended using these components, PCC is being applied.In most situations today, PCC is not applied in terms of the narrative and is not fully elicited or the partnership and/or the documentation are not included.It is proposed that the challenge to Society arising from changing demographics can be addressed by implementing PCC and creating an alternative to existing healthcare.The importance and benefits of such an approach on a wider scale is not yet clear as research has been limited to date.Studies in selected patient populations (heart failure and hip fractures), however, have shown promising results.As the population ages, there will be a dramatic increase in healthcare consumption.Even with technological developments, there will be a need for tremendous resources to be dedicated to care.A new organization and attitude from healthcare policymakers and providers above and beyond the present model appears required in order to respond to this demand.As part of such change, personcentred care, with the interaction between healthcare providers and the person of the patient, can facilitate, compensate and develop more effective healthcare services for the future.
Thrombin activation may be a higher risk for complications and restenosis after percutaneous transluminal coronary angioplasty in unstable patients than in patients with stable angina pectoris. The effects of heparin may be partly counteracted by a decrease in antithrombin (III). The primary objectives of this study were to evaluate whether a subnormal antithrombin level was associated with a hypercoagulable state and to evaluate the effects of antithrombin supplementation, before and after percutaneous transluminal coronary angioplasty, on biochemical signs of coagulation activation. Secondary objectives were to evaluate acute complications and restenosis rate at 3 months. In a double-blind pilot study, 50 patients with unstable angina, with ongoing heparin infusion and with subnormal antithrombin levels (<85%) were randomized to receive antithrombin supplementation or placebo. Treatment targeted to an antithrombin level of 120% was started with a 2 h intravenous infusion before the percutaneous transluminal coronary angioplasty and was repeated, if there were further subnormal values, every 12th hour for 48 h. Angiographic success was 20/25 in the antithrombin group and 21/25 in the placebo group (ns). Abrupt closure occurred in two and one patients in the two groups, respectively. Activation of coagulation measured as elevations of prothrombin fragment 1+2, thrombinantithrombin complexes and fibrin D-dimer was seen 2 days after the procedure. Baseline levels of fibrin D-dimer were 68 ± 69 μg. 1−1 in the antithrombin group vs 71 ± 46 μg. 1−1 in the placebo group (ns). Two days after percutaneous transluminal coronary angioplasty the levels increased to 135 ±103 vs 242 ± 150 μg. 1−1, respectively (P<0·05 between the groups). Restenosis at 3 months occurred in 4/20 antithrombin patients and in 8/21 placebo patients (ns). In unstable angina patients with heparin treatment and subnormal antithrombin levels, antithrombin supplementation resulted in less activation of coagulation and a tendency towards less restenosis.
