Twelve-month efficacy and safety of the conversion to everolimus in maintenance heart transplant recipients

Table 1 Baseline characteristics of the study population and immunosuppression before conversion to everolimus (n = 222)

	n (%)	Mean ± SD
Recipient age (yr)	-	53 ± 10.5
Sex
Male	189 (85%)	-
Female	33 (15%)	-
Mean time from transplant to conversion (yr)	-	8.1 ± 4.5
Type of transplant
First transplant	215 (96.7%)	-
Re-transplant	6 (2.8%)	-
Multiorgan transplant	1 (0.4%)	-
Reasons for transplanta
Ischaemic myocardiopathy	114 (51%)	-
Dilated myocardiopathy	74 (33%)	-
Valve disease	14 (6%)	-
Othersb	16 (7%)	-
Donor age (yr)	-	32.2 ± 12.7
Donor positive for CMV serologyd	106 (48%)	-
Recipient positive for CMV serologye	155 (70%)	-
Pre-transplant risk factorsc	139 (63%)	-
Arterial hypertension	55 (25%)	-
Diabetes	36 (16%)	-
Renal failure	4 (2%)	-
Osteoporosis	3 (1%)	-
Hypercholesterolaemia	29 (13%)	-
Dyslipidaemia	29 (13%)	-
Smoking	23 (10%)	-
Baseline immunosuppression
CNI	210 (95%)	-
CsA	152 (72%)	-
Dose, mg/d	-	142.3 ± 51.6
Blood levels, ng/mL	-	126.1 ± 50.9
Tacrolimus	58 (28%)	-
Dose, mg/d	-	2.9 ± 1.8
Blood levels, ng/mL	-	8.3 ± 4.0
Antimetabolite	189 (85%)	-
MMF	143 (76%)	-
Dose, mg/d	-	1.446.1 ± 499.0
Blood levels, ng/mL	-	2.9 ± 1.7
MFS	8 (4%)	-
Dose, mg/d	-	742.5 ± 413.1
Blood levels, ng/mL	-	3.8 ± 1.7
Azathioprine	38 (20%)	-
Dose, mg/d	-	84.9 ± 46.5
Blood levels, ng/mL	-	-
Corticosteroids	154 (69%)	-
Dose, mg/d	-	5.2 ± 4.2
SRL	21 (9%)	-
Dose, mg/d	-	5.8 ± 2.5

SD: Standard deviation; CMV: Cytomegalovirus; CNI: Calcineurin inhibitor; CsA: Cyclosporine; SRL: Sirolimus; MFS: Mycophenolate sodium; MMF: Mycophenolate mofetil;

^aNot available in 4 patients;

^bCongenital defects, hypertrophic myocardiopathy and acute myocarditis in two patients each, the rest in only one patient;

^cPatient may present multiple risk factors;

^dNot known in 44 patients;

^eNot known in 28 patients.

Table 2 Reasons for conversion to everolimus

Reason for conversion	Percentage	95%CI
Nephrotoxicity	30.00%	24.0-36.0
CAV	20.50%	15.2-25.8
Malignancy	17.20%	12.1-21.9
Nephrotoxicity + CAV	9.80%	5.9-13.7
Nephrotoxicity + neoplasms	7.00%	3.6-10.4
CAV + malignancy	2.00%	0.2-3.8
Others	13.00%	8.6-17.4

CAV: Chronic allograft vasculopathy.

Table 3 Immunosuppressive regimens 12 mo after conversion to everolimus

Immunosuppressor regimen	n (%)	95%CI
Overall study population	n = 1471
EVL + tacrolimus + MMF ± corticosteroids	11 (7.5%)	3.2-11.7
EVL + CsA + MMF ± corticosteroids	7 (4.8%)	1.3-8.2
EVL + tacrolimus ± corticosteroids	11 (7.5%)	3.2-11.7
EVL + CsA ± corticosteroids	67 (45.6%)	37.5-53.6
Total with CNIs	96 (65.3%)	57.6-73.0
EVL + MMF ± corticosteroids	44 (29.9%)	22.5-37.3
EVL + corticosteroids	7 (4.8%)	1.3-8.2
Total without CNIs	51 (34.7%)	27.0-42.4
Patients converted due to nephrotoxicity	n = 66
EVL + tacrolimus + MMF ± corticosteroids	3 (4.5%)	0.1-9.6
EVL + CsA + MMF ± corticosteroids	5 (7.6%)	1.2-14.0
EVL + tacrolimus ± corticosteroids	3 (4.5%)	0.1-9.6
EVL + CsA ± corticosteroids	23 (34.9%)	23.4-46.3
Total with CNIs	34 (51.5%)	39.5-63.6
EVL + MMF ± corticosteroids	27 (40.9%)	29.0-52.8
EVL + corticosteroids	5 (7.6%)	1.2-14.0
Total without CNIs	32 (48.5%)	36.4-60.5

¹The missing values correspond to other combinations or to values not contained in the database. EVL: Everolimus; MMF: Mycophenolate mofetil; CsA: Cyclosporine; CNIs: Calcineurin inhibitors.

Table 4 Adverse events with everolimus

Adverse event	n	% total events (95%CI) (n = 152)	% total evaluable patients (95%CI) (n = 222)
Oedemas	27	17.8% (11.7-23.8)	12.2% (7.9-16.5)
Infections	20	13.2% (7.8-18.5)	9.0% (5.2-12.8)
Gastrointestinal disorders	13	8.6% (4.1-13.0)	5.9% (2.8-8.9)
Skin disorders	12	7.9% (3.6-12.2)	5.4% (2.4-8.4)
Haematological disorders	10	6.6% (2.6-10.5)	4.5% (1.8-7.2)
Pericardial effusion	6	3.9% (0.9-7.0)	2.7% (0.6-4.8)
Pneumonitis	5	3.3% (0.5-6.1)	2.3% (0.3-4.2)
Oral aphthae	3	2.0% (0.2-4.2)	1.4% (0.1-2.9)
Pleural effusion	2	1.3% (0.1-3.1)	0.9% (0.1-2.1)
Healing disorders	2	1.3% (0.1-3.1)	0.9% (0.1-2.1)
Others	52	34.2% (26.7-41.8)	23.4% (17.9-29.0)

Table 5 Reasons for everolimus withdrawal

Drug withdrawal	n	% total patients that discontinue treatment (95%CI) (n = 44)	% total evaluable patients (95%CI) (n = 222)
Oedemas	13	29.5% (16.1-43.0)	5.9% (2.8-9.8)
Gastrointestinal disorders	8	18.2% (6.8-29.6)	3.6% (1.2-6.1)
Bone marrow suppression	4	9.1% (0.6-17.6)	1.8% (0.1-3.6)
Pneumonitis	4	9.1% (0.6-17.6)	1.8% (0.1-3.6)
Skin disorders	2	4.6% (0.1-10.7)	0.9% (0.1-9.5)
Others	14	31.8% (18.1-45.6)	6.3% (3.1-9.5)