Improvement of hypertension and LVH in maintenance hemodialysis patients treated with sustained-release isosorbide mononitrate.
BACKGROUND
Hypertension and left ventricular hypertrophy (LVH) are independent predictors of morbidity and mortality in maintenance hemodialysis (MHD) patients. The level of serum asymmetric dimethylarginine (ADMA) is increased in MHD patients, which is a kind of uremic toxin. It can competitively inhibit nitric oxide production from L-arginine, which can increase vascular resistance, then lead to endothelium dysfunction, hypertension, LVH and decrease of ejection fraction. A sustained-release preparation of isosorbide mononitrate can lead to vasodilatation by releasing nitrogen monoxide. But it remains unclear whether oral isosorbide mononitrate in MHD patients can control blood pressure (BP) and reverse LVH. The aim of the present study was to evaluate the safety and efficacy of oral sustained-release isosorbide mononitrate on hypertension and LVH in MHD patients.


METHODS
One hundred and forty-four MHD patients with hypertension were enrolled in this perspective, randomized, controlled, single-center trial. All patients accepted antihypertensive drugs at baseline, including renin-angiotensin system inhibitor, calcium channel blocker, ß-receptor blocker or a-receptor blocker. Seventy-two patients (nitrate group) took isosorbide mononitrate 30 mg daily, titered to a maximal dosage of 120 mg daily for 24 weeks. The dosage was adjusted once a week according to BP. The remaining 72 patients (non-nitrate group) did not take nitrate drugs other than antihypertensive drugs. BP, left ventricular mass index (LVMI), heart rate, interdialytic weight gain (IDWG) and hemoglobin (Hb) were monitored.


RESULTS
After 4, 8, 12 and 24 weeks of treatment, BP levels decreased in both nitrate and non-nitrate groups. BP in the nitrate group was significantly lower than in the non-nitrate group. But there was no statistical significance in the levels of response rate and control rate of BP between the 2 groups (response rate of BP: 91.4% vs. 86.1%, X2=1.004, p=0.316; control rate of BP: 60.0% vs. 47.2%, X2=2.230, p=0.127). BP before hemodialysis was maintained between 12 and 24 weeks in the nitrate group despite the decrease in total daily category and quantity of hypotensive drugs. At week 24 of treatment, LVMI in the nitrate group was significantly decreased from 65.3 ± 14.2 g/m2.7 to 51.2 ± 10.0 g/m2.7, and that in the non-nitrate group was also significantly decreased from 63.7 ± 16.7 g/m2.7 to 56.1 ± 13.8 g/m2.7. But LVMI in the nitrate group was significantly lower than that in the non-nitrate group. The prevalence of LVH in the nitrate and non-nitrate groups decreased 17.2% and 9.8%, respectively. There was a significant difference in both groups at 24 weeks (X2=4.480, p=0.034). During 24 weeks of follow-up, the incidence of acute left heart failure in the nitrate group was 1.4% (1/70), which was significantly lower than in the non-nitrate group (11.1%, 8/72; X2=5.605, p=0.033). The incidence of adverse events was 1.4%.


CONCLUSIONS
Sustained-release isosorbide mononitrate, which is safe and well tolerated, can effectively control BP, decrease the category and quantity of hypotensive drugs, improve left ventricular hypertrophy and reduce the incidence of acute left heart failure in MHD patients.
Blood Purification Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, PR China.
Han
H
Li
Shi-xiang
SX
Wang
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003692:Delayed-Action Preparations; D005260:Female; D006333:Heart Failure / Q000453:epidemiology / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D015994:Incidence; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects*; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate