The COMPASS trial, investigators tested the hypothesis of noninferiority of three strategies in 27 395 patients with chronic coronary artery disease: (i) rivaroxaban (2.5 mg twice a day) plus aspirin; (ii) aspirin alone (100 mg once a day); and (iii) rivaroxaban alone (5 mg twice a day). The primary end point was a combination of cardiovascular death, stroke, or myocardial infarction. The results showed that the combination of rivaroxaban 2.5 mg twice a day plus aspirin had the best results; however, to achieve a 0.7% absolute reduction in death, 143 patients need to be treated to save one life, and, to reduce major adverse cardiovascular events, 77 patients need to be treated, with an almost similar risk of a major bleeding event. Based on this data, we must determine whether it is necessary to conduct a cost-efficacy study before implementing this treatment.

PEGASUS TIMI 54, another trial similar to COMPASS, included patients with coronary artery disease who had a previous myocardial infarction 1 to 3 years before randomization. PEGASUS TIMI 54, compared three treatments: (i) ticagrelor (90 mg twice a day) plus aspirin; (ii) ticagrelor (60 mg twice a day) plus aspirin; and (iii) aspirin alone with the same primary end point as the COMPASS trial. Compared with aspirin alone, a benefit was observed with both ticagrelor 90 mg twice a day plus aspirin and ticagrelor 60 mg twice a day. While the benefit was similar between the two treatments, ticagrelor 90 mg twice a day plus aspirin resulted in more major bleeding events. 

These results mean that 188 patients need to be treated to prevent 1 cardiovascular death and 79 patients need to be treated to avoid 1 primary end point event, but with a cost of one major bleeding event with this dual antiplatelet treatment. The trial results from both COMPASS and PEGASUS TIMI 54 support using a double antiplatelet or a non-vitamin K-antagonist oral anticoagulant plus aspirin regimen. to reduce cardiovascular events and death; however, as expected, these treatments result in a higher number bleeding events. As such, we need to determine which treatment to choose, if any, and if a treatment is chosen, when it should be given.

Another trial-CANTOS-tested a new treatment strategy to reduce atherosclerotic- sis progression, ie, targeting inflammation using an anti-inflammatory drug. The trial, included 10 061 patients who had all been previously treated with statins to lower cholesterol levels, but who still an excess of inflammation as indicated by a high-sensitivity C-reactive protein level 2.0 mg/L. CANTOS analyzed three doses of canakinumab (50, 150, and 300 mg), a monoclonal antibody against in- interleukin-18, given subcutaneously every 3 months vs placebo for 48 months. The results showed a reduction in major cardiovascular events (3.8% vs 4.5%) with the 150-mg dose vs placebo. In addition, patients in the active treatment arm also had a higher incidence of fatal infections. Considering that 158 patients need to be treated with canakinumab to obtain the reduction in cardiovascular events, but with no reduction in the number of deaths and a cost that is estimated to be $40000 per year, is this treatment really cost-effective?

In addition to the three trials previously discussed, another trial-FOURIER- showed a reduction in cardiovascular events when treating patients with an antibody against the PCSK-9 proprotein. The FOURIER trial was published in March 2017 and presented at the ESC congress in August. The trial provided data about prespecified safety concerns and showed no problems with the very low levels of LDL cholesterol achieved with the treatment. Based on data from studies with the PCSK-9 proprotein antibody, Arieta A et al, conducted a cost-benefit analysis showing that the cost for an additional quality-adjusted life year was $337729. 25 Ollect antiges.

When we see the net effect in all trials, they are near a 0.8% to 1.8% absolute reduction for all events. For example, in the COMPASS trial, almost 150 patients needed to be treated to save one life, which is similar to the results from the PEGASUS trial (NNT-188). So, can we afford these costs? Or should we think about these results differently? The best way to determine which treatment to prescribe would not include thinking about money, but, unfortunately, to have a longer life and/or an improved quality of life someone must pay the costs.

Cost-effectiveness is calculated by health care systems to determine whether they will or will not spend money for a treatment. Obviously, there are many possibilities, which vary by country depending on the available resources in each country or health care system. However, there is no calculation for cost-effectiveness that considers quality of life and well-being instead of available resources, even if we consider that medicines or actions improve people's lives. While some studies have compared interventions (eg, CABG) with angioplasty and clinical treatment or renal transplantation or on-pump CABG with off-pump CABG in terms of cost-effectiveness, other studies have compared an intervention with no intervention in terms of quality of life. However, in chronic coronary artery disease, no study has calculated the cost-effectiveness of the combination of drugs that prolong life. with the necessity and costs of the drugs that alleviate the symptoms of angina, in other words, quality of life, even though drugs are available that improve quality of life by decreasing angina attacks at a relatively low cost (eg, trimetazidine [es- pecially], ivabradine, ranolazine, and B-blockers).

If we could find a way to calculate the cost-benefit ratio of a longer lifespan together with the quality of life, then we could have a better decision-making tool because, for many patients who suffer from a disease, a longer life may mean a lower quality of life. New therapeutic strategies must be developed with this concept in mind because more often we will see a very small decrease in mortality in clinical trials, but at a much higher cost.