[Show abstract][Hide abstract] ABSTRACT: Reports on quality of life of kidney donors include small populations with variable response rates. The aim was to evaluate quality of life in kidney donors in a large cross-sectional study. Through the Norwegian Renal Registry we contacted all 1984 kidney donors in the period 1963-2007 with a response rate of 76%. All received the Short-Form-36 (SF-36) survey form and a questionnaire specifically designed for kidney donors. SF-36 scores for a subgroup (n = 1414) of kidney donors were not inferior to a general population sample, adjusted for age, gender and education. When asked to reconsider, a majority stated that they still would have consented to donate. Risk factors for having doubts were graft loss in the recipient (OR 3.1, p < 0.001), medical problems after donation (OR 3.7, p < 0.001), unrelated donor (OR 2.2, p = 0.01) and less than 12 years since donation (OR 1.8, p = 0.04). Older age at donation was associated with lower risk (OR 0.98, p = 0.03). Compared with other donors, those expressing doubts had inferior SF-36 scores. Norwegian kidney donors are mostly first-degree relatives. They are fully reimbursed and offered life-long follow-up. All inhabitants are provided universal healthcare. This should be considered when extrapolating these results to other countries.
American Journal of Transplantation 06/2011; 11(6):1315-9. DOI:10.1111/j.1600-6143.2011.03517.x · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is considered safe to donate a kidney if internationally accepted medical criteria are fulfilled. However, some donors have encountered hypertension, proteinuria and impaired renal function after donation. The study was based on retrospective data on 908 donors, donating in the period 1997-2007. Preoperative and follow-up data were collected from patient files and the Norwegian Living Donor Registry. Follow-up data were available for 665 donors at 1 year after donation, and 256 donors at 5 years after donation. We calculated the estimated glomerular filtration rate (eGFR) using the four variable Modification of Diet in Renal Disease equation. At 1 and 5 years after donation, the prevalence of hypertension was 11.7% and 27.1% respectively compared to 2.6% before donation. Proteinuria was present in 3.3% and 1.6% at 1 and 5 years. Mean eGFR was 56.1 ± 10.8 ml/min/1.73 m² at 1 year and 61.0 ± 11.8 ml/min/1.73 m² at 5 years. Mean blood pressure was 122.5 ± 10.6/76.2 ± 7.5 mmHg at donation (n = 908), 124.3 ± 14.2/77.9 ± 8.2 mmHg at 1-year (n = 649) and 127.2 ± 15.4/78.8 ± 8.3 mmHg at 5-year follow-ups (n = 247). We found no evidence of further decline in renal function beyond the initial decrement following nephrectomy.
Transplant International 01/2011; 24(1):73-7. DOI:10.1111/j.1432-2277.2010.01148.x · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract A 25-year-old man presented with severe hypertension associated with hypokalemia, elevated plasma renin level and secondary hyperaldosteronism. Malignant phase hypertension and renal artery stenosis were ruled out, and a preoperative diagnosis of renin-secreting renal tumour was made on the basis of higher concentrations of renin in the left than in the right renal venous plasma in spite of normal findings on selective renal arteriography. By removal of the affected kidney the tumour was found and it had a very high content of renin. Following the operation the plasma renin level, serum aldosterone concentration and BP became normal. We present a histopathological description and an ultra-structural study of the tumour.
Journal of Internal Medicine 04/2009; 197(1‐6):329 - 335. DOI:10.1111/j.0954-6820.1975.tb04927.x · 6.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The new vasodilating agent prazosin has been used in 14 patients with strictly defined refractory hypertension. In the 10 patients who completed the study there was an average reduction in blood pressure of about 20%. Six of these patients became normotensive. During the study only 1 patient had a reduction in renal function, as measured by endogenous creatinine clearance.
Combination of prazosin with other antihypertensive drugs caused no orthostatic hypotension of practical importance. Side-effects were few and negligible in all patients except in 1 who could not tolerate the drug.
Current Medical Research and Opinion 08/2008; 4(s2). DOI:10.1185/03007997609109373 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Calcineurin inhibitor (CNI)-free regimens posttransplantation have been claimed to conserve graft function in addition to reduce the risk factors for cardiovascular and malignant disease in renal transplant recipients.
The primary aim of this prospective, open-label, randomized, parallel-group, single-center study was to compare the effect of complete CNI-avoidance posttransplant (daclizumab + mycophenolate mofetil + prednisolone: Dac-group, n=27) with the standard CNI-based immunosuppressive protocol at our transplant unit (cyclosporine A + mycophenolate mofetil + prednisolone: CsA-group, n=27) on renal function (glomerular filtration rate [GFR] determined as plasma clearance of 51Cr-EDTA) in a selected low immunogenic risk population (DR-matched, PRA-negative de novo cadaveric transplant recipients).
There were no significant difference in GFR at week 10 (P=0.61), but GFR was significantly (P=0.029) lower in the Dac-group (52+/-20 ml/min) at month 12 than in the CsA-group (69+/-29 ml/min). One-year patient and graft survival did not differ between the two groups. Overall acute rejection rate was 70.4% (19/27) in the Dac-group and 29.6% (8/27) in the CsA-group (P=0.006).
The strategy to select DR-matched, PRA-negative de novo cadaveric transplant recipients for a CNI-avoidance protocol was not successful. The incidence of acute rejection was unacceptable high even though anti-CD25 antibody induction as well as initial higher mycophenolate mofetil doses (3 g/day) were applied, and renal function was significantly lower in the CNI-avoidance patients at 1 year. Other strategies need to be examined for avoidance of CNI's in the early posttransplant period.
[Show abstract][Hide abstract] ABSTRACT: Heparin-free haemodialysis (HD) with intermittent saline flushes (ISF) in patients with bleeding risk is widely used. The aim of this study was to investigate if ISF reduce coagulation and clotting in stable patients receiving reduced doses of dalteparin.
Inclusion criteria were stable chronic HD patients >or=18 years of age and haemoglobin >or=11 g/dl. Exclusion criteria were use of warfarin and acetylsalicylic acid. Six HD sessions were evaluated per patient. Dalteparin was given as one bolus dose at start of HD (50% of the conventional dose). In HD number 1, 3 and 5, 100 ml saline solution was flushed through the filter each 30 min. In HD 2, 4 and 6, no ISF were given. Potential clotting in the bubble trap was visually observed each hour and graded on a 4-point scale: 1 = normal, 2 = fibrinous ring, 3 = clot formation and 4 = coagulated system. The dialyser was visually inspected at the end of each session: 1 = normal, 2 = a few blood stripes (affecting less than 5% of the surface fibres), 3 = many blood stripes (more than 5% of the fibres) and 4 = coagulated filter. The coagulation marker PF1+2, the platelet activation marker beta-TG and anti-FXa activity were repeatedly measured during HD.
Six men and two women were included. In four cases (four different patients), HD was stopped due to a coagulated system, all cases on days with ISF performed. Multiple linear regression analyses with repeated measurements showed that ISF adjusted for dalteparin dose/kg significantly increased mean clot in the bubble trap, estimate (B) = 0.717, P = 0.0001 and also showed that ISF increased PF1+2, B = 0.16, P = 0.001 when adjusted for anti-FXa activity and hours of dialysis, whereas beta-TG was only borderline increased, B = 0.09, P = 0.055.
ISF during HD does not alleviate visible clotting or intravascular coagulation activity in stable patients receiving reduced doses of dalteparin and polysulphone dialysers. Whether this applies to unstable patients with increased bleeding risk not receiving any anticoagulation remains to be shown.
[Show abstract][Hide abstract] ABSTRACT: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy.
This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147).
The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively.
Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.
[Show abstract][Hide abstract] ABSTRACT: To investigate possible interactions of the novel immunosuppressant everolimus with cyclosporine, a multicenter, randomized, double-blind, placebo-controlled, dose-escalating phase I study was performed. Everolimus regimens (0.75-10 mg/d) were administered for 28 days to stable renal allograft recipients receiving the microemulsion form of cyclosporine. Steady-state cyclosporine profiles were assessed at baseline on day 0 (cyclosporine alone) and on day 21 with everolimus on steady state. By day 21, mean dose-normalized cyclosporine AUC0-12 increased by 15% in patients receiving placebo. In everolimus-treated patients, mean increases in cyclosporine AUC0-12 ranged from 7% to 43%, which were not significantly different across all dosing cohorts including placebo. Linear regression of everolimus AUC on day 21 versus the increase in cyclosporine AUC0-12 yielded a slope not significantly different from a horizontal line (P = ns). In conclusion, these results suggest that steady-state everolimus exposure over the wide range assessed in this study did not affect steady-state cyclosporine pharmacokinetics.
The Journal of Clinical Pharmacology 08/2005; 45(7):781-91. DOI:10.1177/0091270005277196 · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In living donor (LD) kidney transplantation, a predominance of female-to-male donations has been observed. Gender demographics of living donors and outcomes of LD kidney transplantations in Norway were assessed, as this has not been explored previously.
Data from the Norwegian Renal Registry of first LD kidney transplantations (n = 1319) in the period 1985-2002 were used.
The majority of all LD was female (57.8%; P<0.001), while 62.7% of the recipients were men (P<0.001). Females dominated as donors in the spousal group and the parental group (P<0.0001). However, no gender difference was observed in the parental group when the recipients were <30 years old (P = 0.65). In opposite-sex pairs, female-to-male donations were as expected based on the incidence of end-stage renal disease. Donor sex affected neither the incidence of acute rejections nor graft survival. Serum creatinine was higher in renal allografts from female donors to male recipients in the first 4 years after transplantation. Donor age also had significant impact on graft function measured as serum creatinine.
Gender disparities in LD transplantation result from a higher proportion of female-to-female and a lower proportion of male-to-male donations than expected. Both donor age and donor sex influence graft function during the first years. Graft survival and acute rejection episodes appear not to be affected by donor sex in LD kidney transplantation.
[Show abstract][Hide abstract] ABSTRACT: Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transplant function and development of chronic allograft nephropathy in the ALERT (Assessment of Lescol in Renal Transplantation) study.
ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 mg and 80 mg daily, in renal transplant recipients. Patients were randomized to receive either fluvastatin (N= 1050) or placebo (N= 1052) and followed for five to six years. Renal end points included graft loss or doubling of serum creatinine or death; glomerular filtration rate (GFR) was also measured during follow-up in a subset of patients (N= 439).
There were 283 patients (13.5%) with graft loss, mainly due to chronic rejection (82%), yielding an annual rate of 2.4%. Fluvastatin treatment significantly lowered mean low-density lipoprotein (LDL)-cholesterol levels by 32% (95% CI -33 to -30) compared with placebo, but had no significant effect on the incidence of renal graft loss or doubling of serum creatinine, or decline in GFR throughout follow-up in the whole study population. Neither was any treatment effect by fluvastatin found in any of the subgroups analyzed.
Fluvastatin treatment significantly improves lipid values in renal transplant recipients but has no effect on graft loss or doubling of serum creatinine.
Kidney International 11/2004; 66(4):1549-55. DOI:10.1111/j.1523-1755.2004.00919.x · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Current immunosuppressant regimens need to be improved to prevent acute and chronic graft rejection. The novel macrocyclic immunosuppressant everolimus (Certican, RAD) is currently in clinical development to address this issue.
The primary objective of this multicentre, randomized, double-blind, placebo-controlled, dose-escalating phase 1 study was to evaluate the safety and tolerability of everolimus at four dose levels (0.75, 2.5, 5 and 10 mg/day) in maintenance renal transplant patients receiving cyclosporin and steroids. The secondary objective was to assess the pharmacokinetic profile of two different formulations (capsule and tablet) of everolimus.
Fifty-four subjects were randomized for 4 weeks treatment with everolimus (n = 44) or placebo (n = 10). Dose levels of everolimus between 0.75 and 5 mg daily were well tolerated, permitting dose escalation to the highest everolimus dose of 10 mg daily. At this dose, everolimus was associated with a higher incidence and severity of adverse events, most notably thrombocytopenia. Pharmacodynamic assessment showed a relationship between drug exposure and thrombocytopenia. Notable reversible elevations of cholesterol were also observed at the 10 mg/day dose. Other changes in laboratory evaluations, including triglycerides, were minor, reversible and did not appear to be dose dependent. The bioavailability of the tablet formulation was 2.6-fold higher compared with the capsule, with evidence for dose proportionality over the dose range tested. Within-subject pharmacokinetic variability was low (coefficient of variation: 10-19%); however, between-subject variability ranged from 34 to 60% for AUC and C(max).
These results indicate that up to 5 mg/day everolimus results in a dose-proportional exposure, and is adequately well tolerated in renal transplant recipients receiving cyclosporin and steroids.
[Show abstract][Hide abstract] ABSTRACT: Renal transplant recipients have a greatly increased risk of premature cardiovascular disease. The ALERT study was a multicenter, randomized, double-blind, placebo-controlled trial of fluvastatin (40-80 mg/day) in 2102 renal transplant recipients followed for 5-6 years. The main study used a composite cardiac end-point including myocardial infarction, cardiac death and cardiac interventions. Although reduced by fluvastatin, this primary end-point failed to achieve statistical significance thus precluding analysis of predefined subgroups. Therefore, in the present survival analysis, we used an alternative primary end-point of cardiac death or definite nonfatal myocardial infarction (as used in other cardiac outcome trials) which was significantly reduced by Fluvastatin therapy and permits subgroup analysis. Fluvastatin reduced LDL-cholesterol by 1 mmol/L compared with placebo, and the incidence of cardiac death or definite myocardial infarction was reduced from 104 to 70 events (RR 0.65; 95% CI 0.48, 0.88; p = 0.005). Fluvastatin use was associated with reduction in cardiac death or nonfatal myocardial infarction, which achieved statistical significance in many subgroups. The subgroups included patients at lower cardiovascular risk, who were younger, nondiabetic, nonsmokers and without pre-existing CVD. These data support the early introduction of statins following renal transplantation.
American Journal of Transplantation 07/2004; 4(6):988-95. DOI:10.1111/j.1600-6143.2004.00445.x · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of cytomegalovirus (CMV) infection and disease on long-term outcome after kidney transplantation is still unsettled.
Between 1994 and 1997, 397 consecutive first kidney graft recipients and 74 retransplants were included in the study and followed prospectively until December 31, 2001. CMV infection (CMV pp65 antigenemia) and CMV disease were recorded once weekly during the first 100 days after transplantation. No CMV prophylaxis or preemptive therapy was given. In a multiple Cox proportional hazard model allowing time-dependent covariates, the effects of asymptomatic CMV infection and CMV disease, recipient age and gender, retransplantation, living donor, panel-reactive cytotoxid antibodies, acute rejection, and graft loss were tested on overall mortality beyond 100 days post-transplantation. In a similar analysis, the effect of asymptomatic CMV infection and CMV disease plus other factors were tested on death censored graft loss beyond 100 days.
Median (range) follow up time was 66.6 (<1-86.9) months. The incidence of CMV infection and disease during the first 100 days was 62.8% and 23.4%, respectively. The number of total deaths was 96 (20%), 82 occurred after the first 100 days. Independent risk factors for overall mortality beyond 100 days were asymptomatic CMV infection, RR = 2.90 (95% CI 1.61-5.22) (P= 0.001), CMV disease, RR = 2.50 (95% CI 1.31-4.79) (P= 0.006), both compared to no infection or disease, recipient age, RR = 1.066 per year (95% CI 1.048-1.084) (P < 0.001), and graft loss in the whole study period RR = 7.88 (95% CI 4.75-13.08) (P < 0.001). Asymptomatic CMV infection and CMV disease were not independent risk factors for death censored graft loss, but they significantly reduced graft survival uncensored for death, (log rank P= 0.001, respectively).
Asymptomatic CMV infection and overt CMV disease during the first 100 days increase the risk of recipient mortality beyond 100 days. This raises the question whether CMV prophylaxis should be given routinely after kidney transplantation.
Kidney International 07/2004; 66(1):329-37. DOI:10.1111/j.1523-1755.2004.00735.x · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Following the introduction of cyclosporine as basic immunosuppression in our national transplant programme in 1983, the pool of grafts from living donors (LDs) was expanded 2 years later by also accepting LDs mismatched for 2 HLA haplotypes and living unrelated donors (LURDs), mostly spouses. A policy of approaching family members to promote donation was consistently pursued. During 1983 through 2002, nephrectomy was performed on 1519 LDs without mortality. From 1983 through 1988, our learning phase in managing cyclosporine-immunosuppression, 382 patients received first grafts from LDs. One-year graft survival (GS) rates were 94.4%, 90%, 89%, and 82% in 71 HLA identical, 260 haploidentical, 18 2-haplotypes disparate, and 33 LURD graft recipients, respectively. Corresponding half-lives were 15.8, 10.3, 11, and 9.1 years, respectively. Results improved in 1028 patients receiving first LD grafts from 1989 through 2002. Corresponding 1-year GS rates were 96.6% (n=117), 93.5% (n=650), 90.4% (n=73), and 88.8% (n=188), and half-lives were 30, 13.3, 13.5, and 12.3 years, respectively. Similar GS rates were observed in 109 recipients of repeat grafts from LDs. LDs contributed 44% and 21.6% of all first and repeat grafts transplanted, providing grafts to 11 patients (in 1983) increasing to 23 patients (in 2002) per million population per year (pmp/y). When added to grafts from cadaveric donors, 40 to 48 pmp/y were provided with a first or repeat graft since 1990, thus covering at least 65% of the national need for kidney transplantations.
[Show abstract][Hide abstract] ABSTRACT: About one-quarter of renal transplant patients will suffer from symptomatic cytomegalovirus (CMV) disease if no preventive therapeutic measures are taken. In this prospective, randomized single-centre study pre-emptive therapy with oral ganciclovir is compared with conventional deferred treatment.
Renal transplant recipients (n= 455) over 18 years of age were screened weekly for CMV pp65 antigenaemia during the first 12 weeks post-transplantation. If CMV pp65 antigen in leukocytes appeared within 8 weeks post-transplantation patients were randomized and included in the study. Five patients developed CMV disease before positive CMV pp65, and 14 patients with a positive antigen test developed CMV disease before randomization could take place, all these representing a limitation of the applicability of the results in the overall renal transplant population. Altogether 179 patients were not randomized for various reasons. Eighty patients completed the study, 42 were randomized to receive pre-emptive oral ganciclovir therapy and 38 to conventional deferred treatment (control group).
Time from transplantation to start of ganciclovir capsules was 36 (12-60) days and duration of oral ganciclovir therapy was 49 (27-70) days, median (range). No patient in the pre-emptive treatment group, but nine of 38 patients (23.7%) in the control group, developed CMV disease during the first 12 weeks post-transplantation (P= 0.0009). In the period from 3 months to 1 year post-transplantation, two patients in each group developed CMV disease. There were no significant differences in acute rejection or renal function between treatment groups during the first post-transplant year.
Pre-emptive oral ganciclovir therapy in renal transplant recipients during the first 12 weeks post-transplantation effectively prevents CMV disease during this time period. The incidence of late CMV disease (3 months to 1 year after transplantation) was similar in the two groups, indicating that pre-emptive therapy does not result in late onset of CMV disease.
[Show abstract][Hide abstract] ABSTRACT: Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose (C2) monitoring in maintenance patients. This study evaluates the actual C2 range in stable renal transplant recipients (who underwent transplantation >12 months ago). In addition, we investigated whether underexposure or overexposure to CsA (assessed by C2) affects graft function (as measured by serum [S]-creatinine). All renal transplant recipients in Norway receiving CsA were asked to participate; 1447 fulfilled the criteria. Valid C2 and CsA trough concentration (C0) measurements were performed in 1032 renal transplant recipients (71%) monitored by C0. Target C0 level was 75 to 125 mumol/L. CsA levels were measured using a Cloned Enzyme Donor Immunoassay method, and all analyses were performed in the same laboratory (overall mean [+/-standard deviation] CsA C0=112+/-31 mug/L, CsA C2=697+/-211 mug/L [range 81-1580 mug/L], CsA dose [mg/day]=208+/-61, CsA dose [mg/kg/day]=2.8+/-1.1, and S-creatinine=141+/-58 mumol/L). A univariate analysis of variance showed that patients with C2 levels between 700 and 800 mug/L (n=203, S-creatinine=136+/-49 mumol/L) had significantly lower S-creatinine levels compared with patients with C2 levels greater than 950 mug/L (n=94, S-creatinine=152+/-56 mumol/L) (P<0.02). The same was true for patients with C2 levels less than 450 mug/L (n=95, S-creatinine 141+/-72 mumol/L) (P<0.05) when compared with patients with C2 levels greater than 950 mug/L. There was no significant difference in S-creatinine between patients in the low and intermediate C2 group; 666 patients had C0 levels in the therapeutic range (75-125 mumol/L). A linear regression showed a significant relation between S-creatinine and C2 for these patients (P=0.03). The corresponding relation between S-creatinine and C0 was nonsignificant (P=0.3). Monitoring of C2 in maintenance patients is a valuable tool to detect overexposure to CsA. Until results from prospective studies are available, we recommend C0 in the therapeutic range and reduction in CsA in overexposed patients, aiming at a C2 value between 700 and 800 mug/L.
[Show abstract][Hide abstract] ABSTRACT: Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population.
We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat.
After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups.
Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.
The Lancet 07/2003; 361(9374):2024-31. DOI:10.1016/S0140-6736(03)13638-0 · 45.22 Impact Factor