A multicentered study on management of hypertension and use of antihypertensives for patients undergoing hemodialysis

Introduction

Hypertension (HTN) is defined by persistent elevation of arterial blood pressure (BP). The Seventh Report of the Joint National Committee (JNC7) on the Detection, Evaluation, and treatment of High Blood Pressure (JNC7) classifies adult BP. Patients with diastolic blood pressure (DBP) values <90 mm Hg and systolic blood pressure (SBP) values ≥140 mm Hg have isolated systolic hypertension. A hypertensive crisis (BP >180/120 mm Hg) may be categorized as either a hypertensive emergency or a hypertensive urgency.¹ HTN is the most common modifiable risk factor for cardiovascular diseases (CVD), stroke and renal failure.² It is estimated 55,000 deaths were directly attributable to HTN and it was also considered as an underlying cause in other 3,00,000 deaths (Rosamond et al., 2008). The report of World Health Organization states that high BP is the primary or may be secondary cause in some cases for 50% of renal failure and CVD and subsequent deaths worldwide.³ HTN is a common morbidity in 75% of adults with CVD like myocardial infarction, angina pectoris, coronary heart disease, stenosis, arrhythmias etc. It is the second driving reason for Chronic Kidney Disease (CKD). Regardless of the accessibility of a wide scope of antihypertensive medications, hypertension and its complications are still an important cause of adult morbidity and mortality.⁴ Treatment: BP lowering agents significantly reduces the risk of CVD and death-a reduction of 10 mm Hg systolic BP reduced the risk of CVD by 20%, coronary heart disease by 17%, Stroke by 27%, heart failure by 28% and all other mortalities by 13%. Treatment rates of HTN increased from 65% to 75% and adequate BP control from 40%to 52%.⁵ The primary goal of antihypertensive therapy is to prevent morbidity and mortality in hypertensive patients. Appropriate prescribing of medicines is important for the better outcome of the patients and reduce complications such as CVD, Renal failure.⁶

Chronic kidney disease:

Chronic kidney disease (CKD) is decline kidney function which is age related advanced in HTN, diabetes, obesity and primary renal disorders. Decline in renal function leads to cognitive dysfunction, poor quality of life and prolonged hospitalization.CKD can be measured by Glomerular Filtration Rate (GFR), Albumin Creatinine Ratio.⁷

CKD is classified into 5 stages based on kidney function according to Kidney Disease Outcomes Quality Initiative (KDOQI) CKD classification.

The prevalence of CKD has increased in the period of 1999 to 2007 in developed and also developing countries. The prevalence of 10-13% was seen in the populations of India, China, Japan, Taiwan, Canada and USA.⁹ CKD has a high global prevalence with a consistent estimated global CKD prevalence of between 11 to 13% with the majority stage 3. CKD is an independable risk factor for Cardiovascular diseases.⁷

Patients with hypertension undergoing dialysis:

Patients with End-Stage Renal Disease (ESRD) require health care resources like dialysis and have higher rates of morbidity and mortality. Age, gender, race, nonrenal comorbidity, malnutrition, and dose of dialysis are strong predictors of death among dialysis patients.¹⁰

Hence systolic BP is positively associated with stroke and Coronary Heart Disease (CHD) so thus the control of systolic BP can prevent stroke and CHD in hypertensive and non hypertensive patients. Patients with CKD have more chances to die, largely from CVD. The patients with ESRD have eight times higher rate of mortality compared to general population, with CKD and CVD 50% mortality was accounted. In this particular population maintaining the target BP goal is a challenge. So, the administration of two anti-hypertensives are necessary from the initial stage, especially if the systolic blood pressure (SBP) is ≥150 mmHg. In such cases an anti-renin– angiotensin–aldosterone system (RAAS) drug and either a Diuretic or Calcium Channel Blocker (CCB) are preferred.¹¹

There is a trend to start dialysis earlier in patients with chronic renal failure. The current Dialysis Outcomes Quality Initiative (DOQI) guidelines suggest that dialysis should be started when renal function expressed as weekly Kt/V drops below 2.0.⁸

The CANUSA (Canada-USA study on dialysis) study also showed significantly poorer survival for patients with early initiation of dialysis. And also found that these patients had significantly more comorbidities.¹² Due to the advancements in technology and reliability of dialysis machine, HD can be done at home or outpatient department. However, complication do occur during dialysis due to technical problem combined with comorbid conditions of the patient. The common complications include hypotension and arrythmias which are resolved by fluid balance.¹³ In CKD patients, dialysis is the best method to remove accumulated toxins from the body and improve the quality of life. But this process, by itself, may complicate the condition due to its side effects. Individuals suffering from CKD, who are on dialysis, could be at increased cardiovascular and metabolic risk. There is an urgent need to educate CKD, patients about facts related to the disease, medications, dietary habits, and the various measures required to manage the condition and lead a productive life.¹⁴ Therefore the control and monitoring of HTN in these patients is vital. Though there are certain guidelines (KDOQI) regarding the combination of drugs for different target ranges, but the few other studies stated that HTN is not being controlled and there are huge fluctuations. This requires the pharmacist to intervene and develop strategies, monitor lab tests, follow up, adapt drug dosage, prescription audit aimed towards better patient care and improving quality of life of the patients.

Hence, this study mainly aims in focusing on the management of HTN and use of antihypertensives in patients undergoing dialysis.

Materials and Methods

A prospective observational study was conducted over a period of six months in BGS Gleneagles Hospital, Bangalore and Excel Care Hospital, Bangalore. Patients>18 years whowere undergoing hemodialysis were included in the study. The study was approved by Institutional Ethical Committee of BGS Gleneagles Hospital, Bengaluru and Excel Care Hospital, Bengaluru. All the cases were reviewed and those who met the study criteria were followed and drug therapy details were recorded in the suitable data collection form as per the need of the study. and data was analysis by descriptive statistics.

Results

Table 2 and figure 1 implies that, 37% of patients were on two antihypertensive agent and 17% of them were on no antihypertensives.

According to table 3 and figure 2, Most of the patients are receiving Calcium channel blockers (74.54%), beta blockers (53.63%), alpha blockers (36.36%) and centrally acting alpha agonists (34.54%).

Table 4 and figure 3 implicated that, fluid overload status was found in 16(37.20%) and chills, fever and body pains was found in 2(4.65%) subjects.

Discussion

Table 2 & Figure 1 shows the distribution pattern of No. of antihypertensive agents taken among 123 subjects and it was found that majority 46(37.39%) of patients were on dual therapy, 23 (18.69%) were on triple therapy, 20(16.26%) were on monotherapy, 21(17.07%) among them are not on antihypertensives, indicating that fluid retention in CKD influences the control and require multiple agents to treat and promote control.

Our results were similar to the study conducted Rohini Guptha et.al15 on Study of Prescribing Pattern of Drugs used in treatment of HTN in a Tertiary Care Hospital revealed that majority of the patients were on dual therapy. From table 3 and figure 2, classes of antihypertensives prescribed were Calcium Channel Blockers 82(74.54%) followed by Beta blockers 59(53.63%), alpha blockers 40 (36.36%), Centrally Acting Alpha Agonist 38 (34.54%), Loop Diuretics 24(21.81%), Vasodilator 06(5.45%), Angiotensin Receptor Blocker 04(3.63%) indicating that CCBs were commonly prescribed in majority of the patients. These results supported by the work of Rohini Guptha et.al²² on Study of Prescribing Pattern of Drugs used in treatment of HTN in a tertiary Care Hospital revealed that Calcium Channel Blockers were prescribed to a larger extent compared to other antihypertensives.

From table 4 and figure 3, fluid overload status was observed in 16(13%) followed by hypotension 5(4.06%), hypertension 04(3.25%), breathlessness 3(2.43%), pain at fistula site 02(1.62%), hypoglycemia 02(1.62%), abdominal pain 02(1.62%), weakness, itching and cramps 3(2.43%), and chills, fever and body pains 02(1.62%).Our results were similar to the previous literatures.

Conclusion

Appropriate treatment is associated with the better survival and shortened duration of hospital stay in medical patients with CKD. In this study prescriptions were collected from inpatients. It can be concluded from our study that HTN is more common in males than in female and its prevalence seems to follow an increasing trend with increasing age. Apart from HTN, DM is most commonly observed comorbidity in CKD patients. Calcium Channel Blockers are the highest among the prescribed drugs. The number of prescribed medications increases as the GFR declines in advanced CKD patients. The practice of polypharmacy and prevalence of potential drug-drug interactions are high among the study subjects. Most of these interactions have moderate severity and intradialytic complications were observed. There is a need for special attention for the diagnosis and management of intradialytic complications of HD because such complications could be managed successfully without the need for termination of the dialysis procedure. Hyperkalaemia is more predominantly observed electrolyte imbalance. Physicians and clinical pharmacists should update their knowledge regarding current advances in treatment of ESRD patients in order to detect and avoid harmful effects and to provide effective therapy.

Summary

Out of 123 prescriptions assessed, 38 were female and 85 were male. Most of the patients were under the age group of ≥ 60 years.118 were affected with HTN irrespective of other comorbidities and only 33 were exclusively diagnosed with HTN among which the prevalence of HTN in CKD patients was high in male 80 compared to female 38.

The subjects with number of antihypertensives per prescription was evaluated among which most of them were on dual therapy 37.39%, followed by triple therapy 18.69%, monotherapy 16.26%, and 17.07% were not prescribed with antihypertensives.

Most of the patients are receiving Calcium channel blockers 74.54%, beta blockers 53.63%, alpha blockers 36.36% and centrally acting alpha agonists 34.54%, which implies that these are the preferable or primary choices of antihypertensives in CKD and HTN with other comorbid conditions with respect to safety, efficacy, cost and acceptability by patients.

Out of total subjects, 60.16% were prescribed with 6-10 drugs followed by 22.76% were prescribed with >10 drugs per prescription indicating that average number of drugs per prescription are high. Correlating the age implies polypharmacy which may affect the rationality and outcome. The intradialytic complications observed in this study reveal the conditions like fluid overload status, hypotension, hypertension, breathlessness and other minor problems. This may be due to complexity of blood purification where the blood flows between inner and outer compartments leading to pressure and fluid imbalances.