Читать книгу Practical Cardiovascular Medicine - Elias B. Hanna - Страница 202

Ranolazine blocks the late current of the inward sodium channel (I_Na, phase 0), a channel that is particularly active in ischemia or HF. This reduces intracellular sodium and, subsequently, intracellular calcium through the sodium–calcium sarcoplasmic exchange (opposite to digoxin effect). The main effect of ranolazine is the reduction of diastolic calcium overload, which reduces O₂ consumption and improves

LV relaxation. Moreover, the improvement of LV relaxation reduces LVEDP and the coronary compression, which improves microvascular

function and coronary flow.

Ranolazine has been shown to reduce angina burden, increase exercise duration, and reduce ischemic burden on nuclear imaging, particularly in patients with the most severe or frequent angina, whether used in monotherapy or in combination with other antianginal drugs.^51,52

In the MERLIN-TIMI 36 trial of NSTE-ACS patients, ranolazine added to standard therapy reduced the endpoint of recurrent ischemia or worsening angina. The benefit was most striking in women and in patients with elevated BNP.53-55 Ranolazine has not shown any effect on mortality.

Ranolazine only slightly prolongs QT from I ^K blockade (by 2–6 ms) and does not increase the risk of arrhythmia. The blockade of I_Na serves to shorten the action potential, similarly to the effect of lidocaine, and counteracts the I_K blockade. In fact, in the MERLIN trial, ranolazine significantly reduced the risk of VT, SVT, and AF. In addition, ranolazine appeared to reduce the risk of sudden death in patients with VT lasting over 8 beats in the setting of NSTE-ACS.⁵⁶ However, ranolazine should only be used cautiously in patients with prolonged QT or patients receiving QT-prolonging drugs.

Thus, ranolazine has the advantages of:

 Reduction of ischemia without affecting the systemic pressure or heart rate. It is particularly valuable when systemic pressure or heart rate limits the use of other antianginal agents.

 Improvement of LV diastolic function.

 Reduction of arrhythmias.

 Reduction of HbA1c of ~1% in patients with HbA1c ≥8% (MERLIN analysis).

Ranolazine may be used as initial therapy in patients who do not tolerate β-blockers (alternative to CCB and nitrates), or as additional therapy in patients with persistent angina despite standard therapy.