Background-No data are available on the absolute risk of either venous thromboembolism (VTE) or arterial thromboembolism (ATE) in patients with nephrotic syndrome. Reported risks are based on multiple case reports and small studies with mostly short-term follow-up. We assessed the absolute risk of VTE and ATE in a large, single-center, retrospective cohort study and attempted to identify predictive factors in these patients. Methods and Results-A total of 298 consecutive patients with nephrotic syndrome (59% men; mean age, 42Ϯ18 years)were enrolled. Mean follow-up was 10Ϯ9 years. Nephrotic syndrome was defined by proteinuria Ն3.5 g/d, and patients were classified according to underlying histological lesions accounting for nephrotic syndrome. Objectively verified symptomatic thromboembolic events were the primary study outcome. Annual incidences of VTE and ATE were 1.02% (95% confidence interval, 0.68 to 1.46) and 1.48% (95% confidence interval, 1.07 to 1.99), respectively. Over the first 6 months of follow-up, these rates were 9.85% and 5.52%, respectively. Proteinuria and serum albumin levels tended to be related to VTE; however, only the predictive value of the ratio of proteinuria to serum albumin was significant (hazard ratio, 5.6; 95% confidence interval, 1.2 to 26.2; Pϭ0.03). In contrast, neither the degree of proteinuria nor serum albumin levels were related to ATE. Sex, age, hypertension, diabetes, smoking, prior ATE, and estimated glomerular filtration rate predicted ATE (PՅ0.02). Conclusions-This study verifies high absolute risks of symptomatic VTE and ATE that were remarkably elevated within the first 6 months. Whereas the ratio of proteinuria to serum albumin predicted VTE, estimated glomerular filtration rate and multiple classic risk factors for atherosclerosis were predictors of ATE. (Circulation. 2008;117: 224-230.)
Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non-Q-wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.
Summary
The efficacy and safety of vitamin K antagonists (VKA) are related to the actual level of anticoagulation (given as the international normalized ratio, INR). It is often difficult to maintain an optimal INR over time. We assessed the clinical impact of the individual time spent within INR target range (ITTR) in 2304 consecutive patients with venous thromboembolism. Annual incidences of recurrent thromboembolism and major bleeding were 6·2% and 2·8% respectively. The relative risk (RR) of thromboembolism was 4·5 [95% confidence interval (CI) 3·1–6·6, P < 0·001] at INR < 2·0, for major bleeding it was 6·4 (2·5–16·1, P < 0·001) at INR > 5·0, compared with INR 2·0–3·0. Patients with ITTR < 45% were at higher risk than those with ITTR > 65% (RR 2·8, 1·9–4·3, P < 0·001), while no difference was demonstrated comparing ITTR 45–65% and ITTR > 65% (RR 1·2, 0·7–1·8, P = 0·54). Annual incidences of recurrent thromboembolism were 16·0%, 4·9% and 4·6% at ITTR < 45%, 45–60% and >65% respectively. For major bleeding these were 8·7%, 2·1% and 1·9% respectively. ITTR < 37% during the first 30 treatment days was highly predictive for the total treatment time ITTR < 45% (RR 24·2, 13·5–43·1, P < 0·001). In conclusion, ITTR can be used to identify patients on VKA at risk of recurrent thromboembolism or major bleeding. Since the 30‐d ITTR is highly predictive for total treatment ITTR, these patients can be identified soon after start of treatment.
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