Effects of nisoldipine therapy on myocardial perfusion and neuro-hormonal status in patients with severe ischaemic left ventricular dysfunction

Abstract

The effects of nisoldipine on regional myocardial perfusion and neuro-hormonal status were assessed in a double-blind, placebo-controlled study of 32 patients. All patients had ischaemic left ventricular dysfunction, with a left ventricular ejection fraction between 25% and 35%; per protocol, they were stratified according to concomitant use of ACE inhibitors. After baseline measurements at rest, including single photon emission computed tomography (SPECT) with Tc-MIBI, plasma neuro-hormones (norepinephrine, renin, arginine vasopressin, atrial natriuretic peptide) and echocardiography, the patients were randomized to nisoldipine (core coat tablet, 20 mg once daily; n = 16) or placebo (n = 16). Measurements were repeated after 8 weeks. SPECT data were analysed qualitatively (visual comparison by blinded observer) and quantitatively to derive an index of hypoperfusion representing the percentage of the left ventricular mass with Tc-MIBI activity below normal. At baseline, all patients had left ventricular areas with reduced Tc-MIBI uptake and 29 patients also had increases in plasma neuro-hormones. With nisoldipine, the extent of hypoperfusion (quantitative analysis) was reduced in 8/14 patients vs only 2/14 patients with placebo (P = 0.046, 2-tailed test). The benefit of nisoldipine was similar in patients with or without ACE inhibitor therapy and was also confirmed by the visual analysis of the data. Further, none of the neuro-hormones examined was significantly modified by nisoldipine. Thus, chronically underperfused areas are present at rest in patients with ischaemic left ventricular dysfunction, and nisoldipine significantly improved Tc-MIBI uptake in these areas without evidence of detrimental changes in plasma neuro-hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure Reduction and Cardiovascular Prevention: An Update Including the 2003-2004 Secondary Prevention Trials

“…Calcium-channel blockers reduce left ventricular afterload. However, neuro-endocrine activation in response to arterial vasodilatation, as exemplified by the increase in heart rate induced by nifedipine in the ACTION trial (44), as well as the direct negative inotropic action on the myocardium, may elicit heart failure in predisposed patients (122). Nevertheless, on top of diuretics and/or ACE inhibitors, long-acting dihydropyridines (123,124), diltiazem (125) and verapamil (126) can be used in patients with left ventricular dysfunction to lower blood pressure or to treat angina pectoris.…”

Nisoldipine CC: Clinical Experience in Ischaemic Heart Disease

“…22 Cardiology I997:88(supp! 1 ): [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Melcher/Dens/Currv/Hagel…”

“…Nisoldipine CC in Ischaemic Heart Disease Cardiology 1997:88(suppl 1): [17][18][19][20][21][22][23] As PTCA is accepted as a safe and effective therapy for advanced coronary arterial lesions, it has become a major challenge to discover a drug that is capable of preventing restenosis, which, depending on the criterion used, occurs in 13-60% of treated lesions. Unfortunately, none of the pharmacological strategies tested to date has been entirely successful.…”

“…This is believed to occur because the baroreceptor reflexes are triggered by the rate, and not the extent, of vasodilatation and blood pressure change [15,16], Moreover, the lack of reflex tachycardia or cardiac stimulation, in combination with the high vascular selectivity, suggests that nisoldipine CC does not compromise the ischaemic myocardium. Nisol dipine CC is thus well tolerated in patients with ischaemic heart disease [10,11,17,18] and does not evoke sympa thetic neurohormonal activation in patients with isch aemic left ventricular dysfunction [ 19].…”

“…The DEFIANT-I study showed that nisoldipine CC had anti-ischaemic activity and pro vided a beneficial effect on left ventricular diastolic func tion following myocardial infarction. Most importantly, the drug was well tolerated in this high risk group [17,18], Some of the beneficial effects following myocardial in farction may be due to improved regional myocardial per fusion and improved function in chronically ischaemic but viable areas of 'hibernating' myocardium [19,20]. Thus, prolonged nisoldipine CC therapy has no effect on normal myocardium but improves function in hypokinet ic areas and.…”