Scientific letter Selection of the Best of 2017 in Ischemic Heart Disease

To the Editor,

Here, we summarize 6 salient articles published in 2017 covering various aspects related to ischemic heart disease.

In the area of secondary cardiovascular prevention, there are 3 articles in particular that could prompt significant changes in strategies aimed at reducing long-time risk in patients with ischemic heart disease. First, the FOURIER trial¹ compared the efficacy and safety of evolocumab (a PCSK9 inhibitor) with that of placebo in 27 564 statin-treated patients with atherosclerotic cardiovascular disease and low-density lipoprotein-cholesterol (LDL-C) ≥ 70 mg/dL. During follow-up (median, 2.2 years), the group treated with evolocumab experienced a marked drop in LDL-C (median reduction, 30 mg/dL) and a significant decrease in cardiovascular events (9.8% in the evolocumab group vs 11.3% in the placebo group), without differences in severe adverse effects.

The second article analyzed the antithrombotic regimens of patients with chronic ischemic heart disease. The researchers in the COMPASS trial² randomized 27 395 patients to rivaroxaban (2.5 mg/12 h) plus aspirin (100 mg/d), rivaroxaban (5 mg/12 h), or aspirin (100 mg/d). The study was prematurely stopped (mean follow-up, 23 months) due to the superiority of rivaroxaban plus aspirin in the reduction of the primary outcome (composite of cardiovascular death, stroke, and myocardial infarction) vs aspirin alone (4.1% vs 5.4%; P < .001). Although the combination strategy was accompanied by higher incidence of major bleeding (3.1% vs 1.9%; P < .001), there were no significant differences in intracranial or fatal bleeding.

In addition to novelties in the control of risk factors and optimization of antithrombotic therapy, the CANTOS clinical trial³ has put the focus back on inflammation as a key element in the genesis of residual risk in stable ischemic heart disease. The study evaluated the efficacy and safety of canakinumab (monoclonal antibody inhibitor of interleukin-1) vs placebo in 10 061 patients with previous myocardial infarction and persistent inflammatory activity (elevated C-reactive protein). After a 48-month follow-up, patients treated with subcutaneous canakinumab 150 mg every 3 months had lower incidence of the composite primary end point (cardiovascular death, stroke, and cardiovascular events) than those treated with placebo (3.86 vs 4.50 events per 100 person-years; hazard ratio [HR] = 0.85; 95% confidence interval [95%CI], 0.74-0.98; P = .021).

Regarding acute coronary syndromes (ACSs), a noteworthy study examined myocardial infarction screening in patients attending for chest pain. Boeddinghaus et al.⁴ compared the 4 validated strategies involving high-sensitivity troponin I (hs-cTnI): limit of detection (hs-cTnI < 2 ng/L), single cutoff point (hs-cTnI < 5 ng/L), 1-hour algorithm (hs-cTnI < 5 ng/L and 1-h change < 2 ng/L), and the 0/1-hour algorithm recommended by the European Society of Cardiology (combination of the limit of detection and the 1-hour algorithm). The authors prospectively included 2828 unselected patients who presented with suspected myocardial infarction. The 4 algorithms showed an adequate diagnostic validity, although the single cutoff point was less sensitive than the other 3 algorithms in early presenters (within 2 hours of symptom onset).

The PROSPERO meta-analysis of non-ST-segment elevation ACS, by Jobs et al.,⁵ included 8 clinical trials with 5324 patients randomized to either early or delayed invasive treatment. In the overall analysis, the early invasive strategy failed to improve survival. Nonetheless, this strategy significantly reduced mortality in some prespecified subgroups: those with elevated biomarkers at admission (HR = 0.761; 95%CI, 0.581-0.996), diabetes (HR = 0.67; 95%CI, 0.45-0.99), GRACE score > 140 (HR = 0.70; 95%CI, 0.52-0.95), and age ≥ 75 years (HR = 0.65; 95%CI, 0.46-0.93), even if the interactions among these factors failed to show conclusive results in statistical testing.

Regarding ST-segment elevation ACS, in addition to the recent publication of the new European guidelines, whose breadth surpasses the aims of this letter, the COMPARE-ACUTE clinical trial⁶ was performed to clarify the benefit of PCI of noninfarct-related coronary arteries in patients with multivessel disease. Accordingly, 885 patients with ST-segment elevation ACS and multivessel disease treated with primary PCI of the infarct-related artery were randomized to either fractional flow reserve-guided complete revascularization or no revascularization of noninfarct-related arteries. The patients assigned to the fractional flow reserve-guided complete revascularization had lower incidence of the primary composite end point of cardiovascular death, myocardial infarction, stroke, or repeat revascularization (8% vs 21%; HR = 0.35; 95%CI, 0.22-0.55; P < .001), largely due to the variable new revascularization, defined as urgent revascularizations at any time or elective revascularizations performed within 45 days.