Publications

BACKGROUND

There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease.

METHODS

We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling.

RESULTS

Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR ( P=0.318) or iFR ( P=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR ( P<0.00001) and decreasing iFR ( P<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR ( P=0.849) or iFR ( P=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR ( P=0.693) nor iFR ( P=0.761) modified this effect.

CONCLUSIONS

In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI.

CLINICAL TRIAL REGISTRATION

URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

OBJECTIVES

To investigate the prevalence, predictors and associations between guideline-directed medical therapy (GDMT) and clinical outcomes in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) from eight academic centers in the United States.

BACKGROUND

Evidence for GDMT in patients with AMI comes from randomized controlled trials. The use of GDMT in clinical practice is unknown in this setting.

METHODS

PROMETHEUS is a multicenter observational registry comprising 19,914 patients with acute coronary syndrome (ACS) undergoing PCI. Patients with AMI were divided into two groups based on the prescription of GDMT or not (non-GDMT) at discharge. GDMT was defined according to American College of Cardiology/American Heart Association (ACC/AHA) class I recommendations, specifically, dual antiplatelet therapy, statin and beta-blocker for all AMI patients, and additional ACEI/ARB in patients with left ventricular ejection fraction (LVEF) less than 40%, hypertension, diabetes mellitus (DM) or chronic kidney disease (CKD). The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause death, MI, stroke or unplanned target vessel revascularization (TVR) at 1 year.

RESULTS

Out of 4,834 patients with AMI, 3,356 (69.4%) patients were discharged on GDMT. Patients receiving GDMT were more often younger and male. Compared with non-GDMT patients, GDMT patients had a significantly lower frequency of comorbidities. Predictors of greater GDMT prescription at discharge were ST-segment elevation myocardial infarction (STEMI), and increased body mass index (BMI), whereas hypertension, prior PCI, anemia and CKD were associated with less GDMT prescription. At 1 year, the use of GDMT was associated with a significantly lower incidence of MACE (13.7% vs. 22.5%; adjusted HR 0.68; 95%CI 0.58-0.80; P < 0.001), death (3.7% vs. 9.4%; adjusted HR 0.61; 95%CI 0.46-0.80; P < 0.001), and unplanned TVR (8.4% vs. 11.3%; adjusted HR 0.76; 95%CI 0.61-0.96; P = 0.020). However, there were no significant differences in the incidence of MI (4.3% vs. 7.0%; adjusted HR 0.75; 95%CI 0.56-1.01; P = 0.056), stroke (1.5% vs. 2.0%; adjusted HR 0.79; 95%CI 0.47-1.34; P = 0.384) between the two groups.

CONCLUSION

In a contemporary practice setting in the United States, GDMT was utilized in just over two-thirds of AMI patients undergoing PCI. Predictors of GDMT prescription at discharge included STEMI, BMI and absence of hypertension, CKD, anemia or prior PCI. Use of GDMT was associated with significantly lower risk of 1-year MACE and mortality.

Observations on human and experimental atherosclerosis, biomarker studies, and now a large-scale clinical trial support the operation of immune and inflammatory pathways in this disease. The factors that incite innate and adaptive immune responses implicated in atherogenesis and in lesion complication include traditional risk factors such as protein and lipid components of native and modified low-density lipoprotein, angiotensin II, smoking, visceral adipose tissue, and dysmetabolism. Infectious processes and products of the endogenous microbiome might also modulate atherosclerosis and its complications either directly, or indirectly by eliciting local and systemic responses that potentiate disease expression. Trials with antibiotics have not reduced recurrent cardiovascular events, nor have vaccination strategies yet achieved clinical translation. However, anti-inflammatory interventions such as anticytokine therapy and colchicine have begun to show efficacy in this regard. Thus, inflammatory and immune mechanisms can link traditional and emerging risk factors to atherosclerosis, and offer novel avenues for therapeutic intervention.