Pharmacologic Treatment in Dialysis Patients Hospitalized for Cardiovascular Reasons: Do We Follow the Guidelines?

Abstract

Aim: The aim was to assess if the pharmacological treatment due to cardiovascular causes in dialysis patients is compliant with the European Guidelines. Methods: In total, 110 consecutive end-stage renal disease (ESRD) patients on regular dialysis were enrolled into the study. We divided the population into subgroups with coronary artery disease (CAD), chronic heart failure (CHF) and diabetes mellitus (DM). Results: We gathered information about drugs from 99 patients. The mean age was 61.8 ± 12.9 years (70% of males). There were 37 patients with CAD. Acetylsalicylic acid (ASA) was taken by 89% of the patients with CAD, clopidogrel by 25%, beta-blockers by 70%, angiotensin converting enzyme inhibitors (ACEIs) by 50%, angiotensin receptor blockers (ARBs) by 8%, and statins by 41%. Dual antiplatelet therapy was used after stent implantation (35%). There were 24 patients with CHF. Beta-blockers were taken by 71% of the patients, ACEIs by 45%, statins by 54%, and diuretics by 21% with CHF. There were 36 patients with DM. ASA was taken by 89% of the patients, clopidogrel and ticlopidine by 34%, beta-blockers were taken by 67%, ACE-inhibitors by 55%, and statins by 38% of the population with DM. The patients with DM were taking more ACEIs than those without DM (p = 0.033). DM was associated with a statistically 21% higher odds of ACEI/ARB use, but CHF was associated with no increase in the odds of beta-blocker use and no increase in ACEI/ARB use. Conclusions: Dialysis patients with cardiovascular diseases are given less cardioprotective drugs such as ASA, beta-blockers, ACEIs, ARBs, and statins than they should be given according to the guidelines.

• dialysis
• pharmacological treatment
• acetylsalicylic acid
• beta-blockers
• ACEIs
• ARBs

INTRODUCTION

The medical management of chronic coronary artery disease (CAD), chronic heart failure (CHF), and diabetes mellitus (DM) in dialysis patients should follow that of the general population with the exception of specific attention to drugs that alter clearances in kidney failure (e.g., low molecular weight heparin).¹ In particular, patients should receive acetylsalicylic acid (ASA), beta-blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), statins, and/or calcium-channel blockers (CCBs) as indicated.² Dose adjustments are required for medications that are renally excreted or dialyzed. Unique aspects of management in the dialysis population include: modification of dosing regimens so that cardiovascular medications do not adversely impact the delivery of dialysis and ultrafiltration.²

The aim of our study was to assess if the pharmacological treatment due to cardio-vascular causes is compliant with the European Guidelines.¹

MATERIALS AND METHODS

One hundred and ten consecutive end-stage renal disease (ESRD) patients (36 women), on regular dialysis admitted between January 2002 and December 2007 to the Department of Cardiology and the Department of Invasive Cardiology of the Medical University in Bialystok, Poland, were analyzed in this retrospective study. The patients started regular dialysis between 1999 and 2005 (88% of them started a hemodialysis and 12% a peritoneal dialysis). Chest pain was an indication for the admission to the hospital. Medical history was recorded and all the patients underwent physical examination, resting ECG and transthoracic echocardiography. All hospitalized patients were offered coronary angiography even asymptomatic patients with diabetes who were candidates for kidney transplantation. Informed consent for coronary angiography was taken during hospitalization. Eighty-seven out of 110 gave their informed consent. The others did not give their informed consent due to fear of possible complications.

We divided our dialysis population into subgroups with significant CAD, with CHF and ejection fraction (EF) on echocardiography below 40%, and subgroup with DM. We analyzed the use of all kinds of drugs given to the patients due to cardiovascular causes including ASA, clopidogrel, beta-blockers, ACEIs, ARBs, statins, CCBs, diuretics, low molecular weight heparin (LMWH), and unfractioned heparin (UH). We also analyzed the use of drugs during percutaneous coronary intervention (PCI) and compared it with the amount of medications used in general population undergoing coronary procedures in our department at that time. The patients from general population were comparable according to age, sex, and type of the procedure. The demographic and clinical data of the patients on regular dialysis is shown in Table 1.

Table 1.  Clinical characteristics of the study population.

Feature	N	% or mean	SD
Men	99	68%
Age	99	61.81	12.94
Hospitalization duration (days)	98	2.43	2.78
BMI (kg/m^2)	68	25.78	5.34
History of PCI	99	29%
History of CABG	99	17%
Dialysis duration (months)	77	42.51	44.30
Hemodialysis	97	86%
Hypertension	99	93%
Diabetes	99	36%
Diabetes type 2	99	32%
Diabetes type 1	99	4%
Insulin use	99	27%
History of NSTEMI	99	18%
History of STEMI	99	11%
History of unstable angina	99	16%
History of acute myocardial infarction	99	17%
History of stroke	99	8%
Systolic RR on admission	96	134.33	24.68
diastolic RR on admission	96	81.09	13.38
HR on admission	96	77.42	16.65
Sinus rhythm	99	83%
Atrial fibrillation	99	12%
LV on diastole (cm)	95	5.21	0.76
LV on systole (cm)	12	4.00	0.95
Interventricular septum (cm)	95	1.32	0.22
RV (cm)	94	2.73	0.48
Posterior wall (cm)	95	1.41	1.24
Left atrium (cm)	95	4.35	0.58
Aorta (cm)	95	3.50	0.38
EF of left ventricle (%)	94	48.05	13.97
RV (cm)	8	3.99	0.38
LV mass (g)	95	421.35	770.01
LV mass index (g/m^2)	95	234.93	441.77
LV hypertrophy on echocardiography: in women, >110 g/m^2; in men, >125 g/m^2	95	95%
WMSI	95	1.37	0.41
Aortic stenosis	94	9%
Aortic insufficiency	94	5%
Mitral stenosis	94	5%
Mitral insufficiency	94	18%
Tricuspid insufficiency	94	14%
WBC × 10^3/μl	82	8.57	5.54
RBC × 10^6/μl	82	3.68	0.84
HGB	82	10.75	1.71
HCT	82	32.58	5.53
PLT count	82	217.24	90.20
Na (mEq/L)	94	135.89	13.86
K (mEq/L)	94	4.83	0.93
Glucose (mg/dL)	49	137.47	66.11
Total cholesterol (mg/dL)	27	167.85	47.65
Triglycerides (mg/dL)	26	140.35	52.06
HDL cholesterol (mg/dL)	25	38.62	12.07
LDL cholesterol (mg/dL)	24	103.71	41.12
CK (IU/L)	64	301.25	512.74
CK –MB (IU/L)	61	45.54	59.24
Troponine (ng/mL)	37	4.33	9.42
CRP (mg/dL)	28	51.97	67.33
APTT (s)	38	41.32	23.00
Protrombine ratio %	45	83.42	18.35
INR	47	1.18	0.23
Fibrinogen (mg/dL)	30	521.64	196.56

Note: BMI, body mass index; PCI, percutaneous coronary intervention; CABG, coronary artery by-pass graft operation; NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction; HR, heart rate; LV, left ventricle; RV, right ventricle; EF, ejection fraction; WMSI, Wall motion score index; WBC, white blood cells; RBC, red blood cells; HGB, hemoglobin; HCT, hematocrit; PLT, platelets; Na, Sodium; K, Potassium; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; CK, creatine kinase; CF–CK, cardiac fraction of creatine kinase; CRP, C-reactive protein; INR, international normalized ratio; APTT, activated partial thromboplastin time.

The study complies with the Helsinki Declaration of 1975, as revised in 2000. The study protocol was approved by local ethics committee.

TRANSTHORACIC ECHOCARDIOGRAPHY

All studies were performed using the Philips Ultrasound System Sonos 5500 (Andover, MA, USA) equipped for harmonic imaging and 3.6 MHz transducer. Wall motion score indexes (WMSI) assessed using the 17 segment model; global contractility and EF were assessed according to the recommendations of the European Association of Echocardiography.³ For each wall segment, motion was scored as 1 (normal), 2 (hypokinetic), 3 (akinetic), and 4 (dyskinetic). WMSI was obtained by dividing the sum of the segment scores by the number of segments scored.

CORONARY ANGIOGRAPHY

Coronary angiography was performed by injection of contrast medium (low osmolarity and low viscosity) via 6 F catheters after 200 micrograms of intracoronary glyceryl trinitrate (ICGTN), filmed at 12.5 frames/s. The procedure was done via femoral route by standard Judkins technique⁴ or radial route. Luminal stenosis more than 75% by diameter was regarded as significant (visual assessment). The PCI procedure was considered successful when the residual stenosis was <30%, in the absence of dissection and thrombosis. Contrast flow through the epicardial vessel was graded using the standard Thrombolysis in Myocardial Infarction (TIMI) trial flow scale of 0–3.

STATISTICAL ANALYSIS

Distribution of every variable was tested with Kolmogorow–Smirnov test. Afterward, the Student’s t-test or the Mann–Whitney U-test was used for statistical analysis where applicable. Additional analysis of correlations between non-categorical variables was performed using Pearson or Spearman tests, where applicable. Data are expressed as means and standard deviations (SD). Relative frequencies are used to present categorical variables. These variables were assessed with χ² test. A p-value of less than 0.05 was considered as statistically significant. The statistic software NCSS 2010 (Kaysville, UT, USA) was used.

RESULTS

The study population consisted in 70% of males. The mean age was 61.8 ± 12.9 years. The mean dialysis duration was 42.5 ± 44.3 months. Twenty-nine percent of the population had myocardial infarction in the past, and 36% suffered from DM (27% on insulin). C Mean duration of DM was 37 ± 21 months. Fifty-one percent of the patients had diabetic nephropathy. Clinical characteristics of the population are shown in Table 1.

The mean number of significantly narrowed coronary arteries was 1.6 ± 1.6. Stenosis of left main coronary artery was present in 16% of the population. Twenty percent had 1-vessel disease, 15% had 2-vessel disease, and 31% had 3-vessel disease.

We were able to gather information about drugs in 99 patients. We analyzed the use of drugs in 3 groups of patients: subgroup with significant CAD, with CHF and EF <40%, and subgroup with DM.

There were 37 patients in the group with significant CAD. Among them, 28% of the patients were in II Canadian Cardiovascular Society (CCS) class and 72% of the patients were in III CCS class; 37% (n = 14) of them had CHF and 97% (n = 36) had DM. ASA was taken by 89% of the patients while clopidogrel (n = 7, 19%) and ticlopidine (n = 6, 16%) were taken by 25%. Dual antiplatelet therapy was used only in the patients after stent implantation (35%). Beta-blockers were taken by 70% of the patients, ACEIs by 50%, ARBs by 8%, and statins by 41%. Enoxaparin for cardiovascular reasons was given to 5% (n = 2) of the patients with the mean dose 40 mg per day. The use of drugs in this group is shown in Table 2.

Table 2.  Medical treatment used by the patients with coronary artery disease (N = 37 patients).

	Number of patients taking drug	Patients (%)	Mean dose (mg)	SD
acethylosalicylic acid	33	89.19	81.08	41.00
clopidogrel	7	18.92	75.00	0.00
ticlopidine	6	16.22	500.00	0.00
enoxaparine	2	5.41	40.00	0.00
amiodarone	1	2.70	200.00	0.00
amlodipine	16	43.24	9.06	2.02
bisoprolol	7	18.92	4.71	36.34
metoprolol	16	43.24	68.75	30.96
carvedilol	3	8.12	27.08	21.95
doxazosine	2	5.41	3.00	1.41
clonidine	3	8.12	0.20	0.04
ramipril	5	13.51	5.50	2.74
enalapril	7	18.92	27.29	34.74
chinapril	2	5.41	6.25	5.30
benazepril	1	2.70	5.00	0.00
perindopril	2	5.41	7.00	4.24
cilazapril	2	5.41	2.5	0.00
losartan	3	8.12	50.00	0.00
isosorbide	10	27.00	71.00	20.25
molsidomine	3	8.12	5.33	2.31
simvastatine	7	18.92	25.71	9.76
atorvastatine	8	21.62	38.75	20.31
omeprazole	13	24.32	33.33	10.00
pantoprazole	2	5.41	80.00	0.00
lansoprasole	2	5.41	30.00	0.00
ranitidine	2	5.41	225.50	106.07
insuline	19	51.35	–	–
gliclazide	2	5.41	70.00	14.14
glimepiride	1	2.70	1.00	0.00
acarbose	1	2.7	300	0.00
furosemide	5	13.51	56.00	21.91
ASA + ADP-antagonists	13	35.14

There were 24 patients with CHF and EF <40%. Sixty-three percent of the patients were in II class and 37% of the patients were in III class according to New York Heart Association (NYHA). Fifty-four percent of the patients underwent invasive procedures either PCI or CABG and 50% had DM. Beta-blockers were taken by 71% of the patients, ACEIs by 45%, statins by 54%, and diuretics by 21% of the patients with residual diuresis. The use of drugs in this group is shown in Table 3.

Table 3.  Medical treatment used by the patients with diabetes mellitus (N = 36).

	Number of patients taking drug	N or mean (%)	Mean dose (mg)	SD
acethylosalicylic acid	33	89.19	81.08	41.00
clopidogrel	6	16.67	75.00	0.00
ticlopidine	6	16.67	500.00	0.00
enoxaparine	2	5.56	40.00	0.00
amiodarone	1	2.28	200.00	0.00
amlodipine	15	41.67	9.33	1.76
bisoprolol	6	16.67	20.58	39.44
metoprolol	15	41.67	71.67	29.68
carvedilol	3	8.33	27.08	21.95
doxazosine	2	5.56	3.00	1.41
clonidine	3	8.33	0.20	0.04
ramipril	5	13.89	5.50	2.74
enalapril	7	19.44	27.29	34.74
chinapril	2	5.56	6.25	5.30
benazepril	1	2.78	5.00	0.00
perindopril	2	5.56	7.00	4.24
cilazapril	2	5.56	2.50	0.00
losartan	3	8.33	50.00	0.00
isosorbide	9	25.00	67.78	18.56
molsidomine	2	5.56	4.00	0.00
simvastatine	7	19.44	25.71	9.76
atorvastatine	7	19.44	38.57	21.93
omeprazole	9	25	33.33	10.00
pantoprazole	1	2.78	80.00	0.00
lansoprasole	2	5.56	30.00	0.00
ranitidine	2	5.56	225.00	106.07
insuline	19	52.78
gliclazide	2	5.56	70.00	14.14
glimepiride	1	2.78	1.00	0.00
acarbose	1	2.78	300	0.00
furosemide	5	13.89	56.00	21.91
ASA + ADP-antagonists	12	33.33

Table 4.  Medical treatment used by the patients with chronic heart failure (N = 24).

	Number of pts taking drug	N or mean (%)	Mean dose (mg)	SD
acethylosalicylic acid	20	83.33	75.00	0.00
clopidogrel	11	45.83	75.00	0.00
ticlopidine	4	16.67	500.00	0.00
enoxaparine	3	12.50	50.00	17.32
amiodarone	1	4.17	200.00	0.00
amlodipine	7	29.17	9.29	1.89
verapamil	1	4.17	80.00	0.00
bisoprolol	6	25.00	20.38	39.54
metoprolol	11	45.83	61.36	39.31
ivabradine	1	4.17	15.00	0.00
clonidine	2	8.33	0.23	0.00
ramipril	3	12.00	3.33	1.44
enalapril	1	4.17	2.50	0.00
chinapril	2	8.33	6.25	5.30
benazepril	1	4.17	5.00	0.00
perindopril	2	8.33	3.00	1.41
cilazapril	1	4.17	2.50	0.00
isosorbide	6	25.00	67.50	28.59
molsidomine	2	8.33	6.00	2.83
simvastatine	6	24.00	20.00	0.00
atorvastatine	7	28.00	38.57	21.93
omeprazole	6	24.00	30.00	10.95
pantoprazole	4	16.00	60.00	23.09
lansoprasole	4	16.00	45.00	17.32
ranitidine	1	4.17	150.00	0.00
insuline	10	41.67
glimepiride	1	4.17	1.00	0.00
furosemide	4	16.00	50.00	20.00
spironolaktone	1	4.17	12.5	0.00
ASA + ADP-antagonists	15	62.50

There were 36 patients with DM in the study group. All of them had either PCI or CABG and 35% of them had CHF. ASA was taken by 89% of the patients while clopidogrel (n = 6, 17%) and ticlopidine (n = 6, 17%) by 34% of the population with confirmed CAD. Dual antiplatelet therapy was used only in the patients after stent implantation (33%). Beta-blockers were taken by 67% of the patients, ACEIs by 55%, ARBs by 8%, and statins by 38%. Insulin was taken by 53% of the patients. The use of drugs in this group is shown in Table 4. The patients with DM were taking significantly more ACEIs than the patients without DM (p = 0.033).

DM was associated with a statistically 21% higher odds of ACEI/ARB use, but CHF was associated with no increase in the odds of beta-blocker use and ACEI/ARB use.

There were no significant differences in the use of beta-blockers between the patients treated with PCI/CABG and those treated conservatively (72.7% vs. 56.4%, p = 0.090), but significantly more patients after PCI/CABG were taking ASA and clopidogrel (p = 0.008 and p < 0.000, respectively).

Medium doses of beta-blockers and ACEIs used by the patients at age <70 years old and >70 years old (p = 0.969 and p = 0.111, respectively) and in patients with average blood pressure value <130/80 mmHg and >130/80 mmHg (p = 0.392 and p = 0.454, respectively) were similar. Medium dose of beta-blocker in patients <70 years old was 82.6 mg/day and in the group >70 years old was 79.9 mg/day. Medium dose of beta-blockers in patients with blood pressure (RR) <130/80 mmHg was 72.0 mg/day and in the group with RR >130/80 mmHg was 80.3 mg/day. We found no significant differences in the use of beta-blockers between the patients with heart rate <70/min and >70/min There were also no differences in using beta-blockers and ACEIs between males and females (p = 0.222 and p = 0.662, respectively).

We also found no significant differences between the use of medication during PCI, apart from intravenous nitroglycerine which was used more frequently in control group than in dialysis patients (23% vs. 40%, p = 0.002).

UH was administered in the following doses: 6591.9 ± 3105.3 in dialysis group and in the control group 6593.0 ± 2760.0 IU (p = 0.346).

DISCUSSION

Patients on dialysis are almost invariably excluded from trials evaluating the cardioprotective effect of novel treatments. Beta-blockers, for example, were shown to prevent sudden cardiac death (SCD) in cardiomyopathy or CAD patients. Pharmacotherapy with beta-blockers also prevents SCD in high-risk dialysis patients.⁵ According to Matsue et al.,⁶ beta-blocker use in hemodialysis patients was not only associated with lower risks of SCD but also death from all causes on 4.9 years follow-up. In our population, 70% of the patients with CAD and 71% of the persons with CHF were given beta-blockers on discharge from hospital while the guidelines on CAD¹ and CHF⁷ recommend them in every patient without contraindications.

Surprisingly, Kitchlu et al.⁸ in a large retrospective study (1836 patients) showed that only high-dose beta-blocker therapy was associated with better cardiovascular outcomes. In our study, we recorded rather low mean doses of daily beta-blockers: 4.7 mg of bisoprolol, 68.8 mg of metoprolol, and 27.1 mg of carvedilol.

ACEIs are recommended for patients on dialysis.² In our population with 93% of patients with hypertension, 51% of the patients with CAD, 41% of the persons with CHF, only 53% were given ACEIs on discharge from hospital. Additionally, 8% of population with CAD and 8% of patients with DM received ARBs. According to the guidelines⁹ diabetic patients should be prescribed a rennin–angiotensin system inhibitors as part of the blood pressure lowering treatment (I A class of recommendations). Screening for microalbuminuria and adequate blood pressure-lowering therapy including the use of ACEIs and ARBs improve micro- and macrovascular morbidity in type 1 and type 2 DM (I A class of recommendations). The above mentioned rates of use of cardiovascular drugs in our study seem to be low while clear evidence is available that ACEIs and ARBs reduce morbidity and mortality in patients on dialysis with CHF or atrial fibrillation. Moreover, these drugs also show an excellent tolerability profile in this population.¹⁰

According to Gamboa et al.,¹¹ ramipril in dialysis patients increased IL-1β concentrations and decreased IL-10 concentrations compared with placebo. Valsartan and ramipril both lowered IL-6 levels during dialysis. During hemodialysis, valsartan induces a greater anti-inflammatory effect compared with ramipril, although ramipril seems to prevent dialysis-induced endothelial dysfunction, as measured by levels of von Willebrand factor (vWf).¹¹ Treatment with ACEIs or ARBs reduced LV mass in patients receiving hemodialysis. However, their use was not associated with a statistically significant reduction in the risk of fatal and nonfatal CV events.¹² Moreover, according to Chang et al.,¹³ in a cohort of patients on hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity. The higher risk of heart failure hospitalization associated with ACEI use may highlight gaps in evidence when applying treatments proven effective in the general population to patients with end-stage renal disease (ESRD).^13,14

Statins have demonstrated to effectively and safely reduce cholesterol levels in chronic kidney disease patients.¹⁵ In our population, 41% of the patients with CAD, 54% of the persons with CHF, and 38% patients with DM were given statins on discharge from hospital. The authors of the European Guidelines strongly recommend administering statins to every patient with CAD (I A class of recommendations). In diabetic patients with cardiovascular diseases, statin therapy should be initiated regardless of baseline LDL-cholesterol concentration (I A class of recommendations). According to Lee et al.,¹⁶ statins were prescribed for 37.8% of incident peritoneal dialysis patients. Statin prescription was associated with a 41% lower adjusted hazard ratio of death in the unmatched cohort. The protective effect of statins was also observed in a subgroup analysis of patients with diabetic ESRD. The association between use of statins and mortality is still a matter of discussion. In patients with type 2 DM undergoing hemodialysis, atorvastatin significantly reduces the risk of fatal and nonfatal cardiac events and death from any cause if pretreatment LDL-cholesterol is >145 mg/dL (3.76 mmol/L).¹⁷

Nevertheless first prospective 4D study¹⁸ which assessed efficacy of atorvastatin in 1255 patients with type 2 diabetes revealed that the use of atorvastatin did not decrease the rate of cardiovascular deaths, myocardial infarctions, and strokes, although it decreased LDL-cholesterol concentration.

Statins have pleiotropic effects such as anti-inflammation. High-sensitive C-reactive protein (CRP) levels were significantly decreased in statin users compared with nonusers.¹⁹

Kirmizis et al.²⁰ found that in hyperlipidemic hemodialysis patients, simvastatin treatment resulted in a significant reduction in markers of endothelial dysfunction, inflammation, oxidative stress, endothelial cell apoptosis, and peripheral blood monocyte stimulation. A decrease in the TNF-alpha level could be one of the possible mechanisms of the anti-atherogenic effect of simvastatin.²¹ Furthermore, treatment with simvastatin downregulates enhanced CD40–CD40 ligand interactions in peritoneal dialysis patients.²² Simvastatin also favorably affects platelet aggregation and the extrinsic coagulation pathway and improves fibrinolysis; thus, it might reduce the risk of thrombotic complications in peritoneal dialysis patients.²³

European Guidelines on CAD¹ let clinicians know which medications are contraindicated or not recommended for use in specific patient groups. Little is known about the use of certain antiplatelet and antithrombotic medications and their effects on outcomes in clinical practice in dialysis patients. According to Tsai et al.²⁴ who gathered data on 22,778 dialysis patients, 22.3% of them received a contraindicated antithrombotic drugs during PCI. Among these patients, 46.7% received enoxaparin, 64.1% received eptifibatide, and 10.9% received both. Receipt of these medications was significantly associated with an increased risk of in-hospital major bleeding. There is a prolonged time course to the restoration of normal platelet aggregation in patients with severe renal dysfunction who are treated with eptifibatide.^25,26 Acute renal hemodialysis may reverse the inhibitory effect of eptifibatide on platelet aggregation in these patients. In our population, no one was given eptifibatide.

UH remains the most commonly used anticoagulant for extracorporeal therapies worldwide due to cost, years of clinical experience showing effectiveness, and safety for outpatient hemodialysis.²⁷

LMWH have become very popular in Western Europe for routine outpatient hemodialysis sessions due to the reliability of their clinical effect, ease of administration, and low cost.²⁸ Enoxaparin in our population was given for 5% of the patients with CAD, 12.5% of the patients with CHF, and 16.67% of the patients with DM between dialysis sessions for cardiovascular reasons. The dose was low—40 mg per day. The long-term effects of enoxaparin on the platelet count, according to Brophy et al.,²⁹ were comparable to UH.

How often are certain groups of drugs used in dialysis population? Wetmore et al.³⁰ analyzed a very large cohort of 48,882 hypertensive long-term dialysis patients. Persons on dialysis had lower use of antihypertensive medications with cardioprotective properties, such ACEIs, ARBs, and beta-blockers than might be expected. In multivariable analyses, cardioprotective antihypertensive medication exposure was associated significantly with younger age, female sex, nonwhite race, and intact functional status. Diabetes was associated with a statistically higher odd of ACEI/ARB use, but CHF was associated with only 9% increase in the odds of beta-blocker use and no increase in ACEI and ARB use. There was substantial state-by-state variation in the use of all classes of agents, with a greater than 2.9-fold difference in adjusted-rate odds ratio (ORs) between the highest and lowest prescribing states for ACEIs/ARBs and a 3.6-fold difference for beta-blockers. In our study, DM was associated with a statistically 21% higher odds of ACEI/ARB use, but CHF was associated with no increase in the odds of beta-blocker and ACEI/ARB use.

Giverhaug et al.³¹ provided an overview of the degree of treatment goal achievement and drug prescribing in patients with CAD from general population in clinical practice. In two hundred patients undergoing planned or acute PCI, 78% was on a statins and 92% were on aspirin in their drug regimen. Five out of 16 patients with DM included in the study were given ACEIs. The study showed relatively low rate of prescribed cardioprotective drugs. There is a potential for improved drug prescribing in dialysis patients with CAD, CHF, and DM.

Clearly, the underutilization of pharmacologic therapies in CAD/ACS patients with CKD is now well established. The question arises how we can explain this phenomenon.

Since CAD/ACS therapies have not been well studied in patients with CKD, they were not accepted as “standard of care” by many physicians. Many doctors fear of prescribing the cardioprotective drugs due to their side effects, which could be aggravated by the hematologic, metabolic, and endocrinologic abnormalities present in CKD. A classic example is the concern regarding antiplatelet therapy—aspirin and thienopyridines—in CKD patients who tend to manifest anemia and platelet dysfunction. Many drugs require dose modification according to kidney function. Another practical issue should be taken into account, patients with CAD and CKD are often co-managed by cardiologists and nephrologists with different practice styles and different guidelines. In addition, our population of patients with CAD and CKD is getting older and older. They are prescribed more and more drugs for many other comorbidities; therefore, interactions, compliance, and financial issues should be kept in mind. Drugs prescribed do not necessarily mean drugs taken.

Finally, in the recent years, nephrology is full of nonpositive trials; the landmark trilogy of statin trials in CKD [a study to evaluate the use of rosuvastatin in subjects on regular hemodialysis (AURORA), Die Deutsche Diabetes Dialyze Studie (4D), and study of heart and renal protection (SHARP)] did not prove a reduction in mortality in this population, making nephrologists somehow reluctant to extrapolate all the data from cardiology into their daily practice pattern.

CONCLUSIONS

Dialysis patients with cardiovascular diseases are given less cardioprotective drugs such as ASA, beta-blockers, ACEIs, ARBs, and statins than they should be given according to the current guidelines. There were no differences in drug use during PCI among patients receiving chronic dialysis compared to non-dialysis group.

STUDY LIMITATIONS

As our study population came from a single dialysis center, belonging to the same Medical University, we enrolled the relatively small number of patients. The study is a retrospective one.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.