Is the Pleotropic Effect of Ranolazine is Due to its Antioxidant Action
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BACKGROUND: Ranolazine is indicated as antianginal drug. We observed that it has other pleotropic effects also. So, we want to study the effect of Ranolazine in improvement of left ventricular (LV) function in obstructive coronary artery (CAD) diseased patients along with ACC/AHA guidelines of treatment. And to see the mode of improvement in LV function is due to its antioxidant effect.
MATERIALS AND METHODS: We recruited CAD patient between the age group 18-80 yrs with LV dysfunction in whom ischemic component was treated. Cases received ranolazine 500 mg two times a day and controls without the drug. Both groups received standard drug therapy according to ACC/AHA guidelines of treatment CAD. For all these patients at basal and at 6 months of follow up, all baseline and demographic parameters, clinical features and symptomatology with blood chemistry parameters were collected. In addition Two Dimensional echocardiography (EF, MAV), Treadmill test (METs) and plasma oxidative stress levels (MDA) will be performed at 0 day (day of recruitment) and at 6 months. MDA concentration was tested by using the method described by Draper and Hadley based on TBA reactivity. Normal Range of MDA is 3.60 ± 0.90 Nano mole/ml.
RESULTS: 100 cases and 40 controls were recruited for this study. Male: Female ratio was 3.4:1 in cases and in controls. The mean age of cases was 56.8 ± 9.6 yrs in cases and 55.1 ± 12 yrs in controls. There was no difference in demographic features and risk factor profile in between the cases and controls expect smoking ( high in cases). Even in echo EF was comparable but MAV is more in cases than controls (9.5 ±2.1 vs 8.8±1.8) which are also not statistically significant.
There is statistically significant improvement of EF either by dimension (48.3 ± 9.6 vs 43.8±8.4 %, p= 0.008) or volume (p=0.018) method of estimation and peak mitral annular velocity in cases (9.8±1,8 vs 8.7± 1.8 cm/sec, p= 0.001) who received additional ranolazine therapy than controls.
MDA at 6 months in cases was decreases to 3.4±0.8 nano mole/dl where as in controls increased to 3.9±0.7 nano mole/dl. Out of 100 cases we could able to get Treadmill test done only for 89 patients with modified Bruce protocol and there was a statistically significant improvement in the number of metabolic equivalents at 6 months in cases comparison to basal exercise capacity (6.8± 2.4 vs 8.2 ± 8.1 METS, p= 0.05).
Ranolazine can act as not only an anti anginal drug but also it was shown to have positive effects on improving LV function (improvement in EF and mitral annular velocities) and improving the exercise capacity (increased METs by TMT). These effects may be due to reduction in the oxidative stress (decreased MDA levels).