Chronic Ischaemia: Time to Review all the Concepts?

The standard approach to treat coronary artery disease (CAD) encompasses two main goals: 1) improvement of prognosis by modification of lifestyle, reduction of risk factors as well as by using aspirins, statins, ACEi, and beta blockers in case of concomitant left ventricular dysfunction and; 2) improvement of angina. This second goal is based on increasing oxygen supply to the myocardium and/or reducing oxygen consumption by means of hemodynamic effects, acting via the heart rate in the case of Ivabradine, or via heart rate and myocardial contractility in the case of beta blockers and verapamil or diltiazem, and via the peripheral arterial coronary and/or venous resistance in the case of dihydropyridine calcium-channel blockers and nitrates. An alternative approach is to improve the efficiency and the energy of the heart for a given supply of oxygen, which is reduced during ischemia. This metabolic approach is achieved by Trimetazidine which does not have hemodynamic effects, but acts as a modulator of cardiac metabolism and could be useful when myocardial ischaemia occurs in absence of obstructive epicardial CAD (i.e. microvascular angina). Another circumstance, in which the coronary arteries might result normal at coronary angiography, is the so called vasospastic angina, which should be treated with calcium channel blockers and nitrates. In the guidelines, symptomatic antianginal agents are classified as first (beta blockers, calcium channel blockers, and short acting nitrates) and second choice (Nicorandil, Ivabradine, Ranolazine, and Trimetazidine) with the recommendation to reserve the second choice medicaments for patients who have contraindications to the first choice agents or who fail to tolerate them or who remain symptomatic.

However, there is no head to head comparison between first and second choice treatment that demonstrates a superiority of one class of drugs versus the other. Meta-analyses show that all antianginal drugs possess similar efficacy and level of evidence in reducing symptoms, while none has shown survival benefits. Newer molecules, which are classified as second choice, actually, have more contemporary evidence based data than the traditional first choice drugs. It is therefore difficult to consider some but not the other as a first choice. In addition, double and triple therapy to control angina is often needed. Patients with angina may have several comorbidities and symptoms may result from different underlying pathophysiologies. Some agents, beside the antianginal effect, have properties which could be useful depending on the different mechanisms of angina and the comorbidities. Guidelines do not provide indication of the best possible combination.

Thus there is the need of more individualized approach for the treatment of angina, which takes into consideration the patient and his comorbidity as well as the underlying mechanism of the disease. A proposal on this regard will be illustrated.