We returned from ACC.17 impressed by the number of clinical trials, the wide array of important clinical studies presented and the impact of many of the trials on the practice of cardiology. Much attention has been focused on the treatment of hyperlipidemia with a monoclonal antibody that blocks PCSK9 and lowers LDL. Previous studies with this class of drug have demonstrated a striking effect on LDL. Now we have data from the FOURIER study that shows lowering LDL with evolucomab translated into a 2 percent lower risk for cardiovascular events in patients with known coronary disease. While statistically significant, the improvement in the event rate is small, and patients may balk at the added cost.

The EBBINGHAUS study examined cognitive function with a battery of cognitive performance tests in a subset of patients from the FOURIER study. The investigators found no changes in cognitive function after 24 months of therapy with evolocumab.

The SPIRE program showed that anti-drug antibodies to another PCSK9 inhibitor, bococizumab, reduced its efficacy in lowering LDL in a substantial number of patients. However, no detrimental effects of bococizomab were found after three years of therapy, and no evidence of cognitive changes were noted from long-term use. Many patients achieve a reasonable LDL goal with a combination of dietary change, a statin and in some cases the addition of ezetimibe. Decisions on the use of a PCSK9 inhibitor in practice will be affected by cost and the reluctance of some patients for periodic self-injections.

ACC.17 provided many insights into how to manage patients with a variety of common disorders.

In the CARAT trial, efforts to raise HDL with the injection of a synthetic HDL failed to reduce atherosclerotic plaque volume and offers yet another failed attempt to reduce atherosclerotic burden by manipulating HDL.

Transcatheter aortic valve replacement (TAVR) received more attention at this year’s meeting. We have moved from high-risk elderly patients who were poor surgical candidates for AVR to moderate-risk patients. Data from the SURTAVI trial indicated that intermediate-risk patients have similar outcomes when undergoing TAVR or surgical replacement (SAVR). This information is welcomed news for many intermediate-risk patients who prefer a non-surgical solution to their aortic valve disease. These findings will require further observation as we expand indications for TAVR. Although small and asymptomatic cognitive changes were found in TAVR patients, these were associated with a higher incidence of MRI-documented cerebral microbleeds in the TAVR group.

Accumulation of thrombus on TAVR valves was examined in the RESOLVE and SAVORY registries. Each registry found significant thrombus on both TAVR valves and surgically implanted bioprosthetic valves, but more thrombus was found on TAVR valves. Anticoagulant therapy, but not antiplatelet therapy, prevented thrombus accumulation, and initiation of anticoagulant therapy reversed thrombus accumulation when it was detected. CT appears more sensitive than echocardiography as a detection tool, as it often identifies early valve thrombosis before a significant gradient develops. No long-term consequences were noted with the accumulated thrombus, but the incidence of transient ischemic attacks was higher when thrombus was present on the valve. We’ll continue to monitor data on valve thrombosis that at present does not appear to be a serious concern if patients are treated with anticoagulation therapy.

The perplexing question of the safety and efficacy of long-term, low-dose direct oral anticoagulant (DOAC) therapy for the prevention of recurrent venous thromboembolism (VTE) was addressed by studies presented at ACC.17. EINSTEIN Choice provides support for low-dose rivaroxaban for long-term VTE prevention, welcomed news for patients on long-term warfarin. Once again, aspirin seems to be less efficacious and continues to show a higher risk for bleeding. Data last year showed that women with a spontaneous deep vein thrombosis (DVT) could stop anticoagulation after a year with no increase in subsequent DVT risk. These studies provide clinicians with several options in managing long-term care for patients with a DVT. Aspirin seems to be the least efficacious when considering prevention of DVT and risk of bleeding.

Looking at antithrombotic therapy in patients with acute coronary syndrome treated with a P2Y12 inhibitor, GEMINI-ACS-1 found no difference between low-dose rivaroxaban and aspirin for bleeding risk or thrombotic events. In atrial fibrillation (AFib), a secondary analysis of data from the ARISTOTLE trial indicated that digoxin may be associated with increased mortality when the digoxin level is above 1.2 ng/mL. An alternate solution to stroke risk with AFib – left atrial occlusion – was supported by data from the STS registry that showed a significant reduction in stroke risk for patients with AFib who had the left atrium closed or amputated during mitral or aortic valve surgery or CABG. The improvement was evident in patients who were not treated with anticoagulation after surgery.

There is no end to the analytic potential of an electronic waveform and a digital computer. A case in point, the iFR-SWEDEHEART group presented data on an alternate measure called the instantaneous wave-free ratio (iFR) to predict the severity of coronary stenosis. The group derived their measure from the aortic pressure wave recorded from the distal pressure catheter inserted to measure fractional flow reserve (FFR) in patients undergoing cardiac catheterization and possible intervention. Their analysis showed a similar predictive value to the FFR, but did not require an intracoronary adenosine injection, eliminating the associated chest discomfort from the vasodilator response. The iFR data were shown to be non-inferior to FFR data, and patients had less discomfort from the IFR procedure.

"While many studies did not show positive results that would change practice, many of the negative trials still provided reassurance that our current approach to cardiology care is on track."

DEFINE-FLAIR addressed a similar comparison between iFR and FFR with similar results and again raises the question of the real-world application of these clinical trial results. This simpler method of stenosis assessment was shown by both studies to provide similar clinical outcomes when compared with FFR measures. The data are encouraging, particularly because iFR-SWEDEHEART provided real-world registry data. Most interventionalists are likely to persist with FFR measures as both methods still require instrumentation of the coronary artery with two catheters for proximal and distal pressure measurement, and both methods can be done during the intervention with minimal additional procedure time and no added risk.

While we still debate the question of complete revascularization versus culprit-vessel PCI in patients with an acute myocardial infarction (MI), the Compare-Acute trial suggests that patients who undergo complete revascularization within 45 days off the initial event have a significantly lower composite cardiovascular outcome rate compared with those who undergo culprit-vessel PCI alone. The data help to resolve this important question in favor of complete revascularization within 45 days after revascularization for an acute MI. However, it is better to manage a totally occluded artery medically as the outcome is no better compared with doing a PCI and the risk of procedural complications is avoided. Data from the DECISION-CTO trial support the medical approach to management of a CTO.

We continue to be stymied by our inability to achieve substantial improvement in the number of individuals with hypertension who receive either no therapy or inadequate therapy. The REACH trial tried again to improve cardiovascular health with use of improved communication in patients being treated for hypertension. The investigators used e-counseling to encourage patients to maintain their medications and to adhere to lifestyle changes that would lower blood pressure. Both the control group and the intervention group showed some improvement in blood pressure, with the intervention group showing a significantly greater response. The data support the important concept that constant communication between patient and provider is an important component of care for patients with hypertension.

ACC.17 provided many insights into how to manage patients with a variety of common disorders. While many studies did not show positive results that would change practice, many of the negative trials still provided reassurance that our current approach to cardiology care is on track. We look forward to future meetings with similar anticipation of new practice-changing studies, as well as the negative studies that assure us that much of our current therapy is up-to-date.

Alfred A. Bove, MD, PhD, MACC, is professor emeritus of medicine at Temple University School of Medicine in Philadelphia, and a former president of the ACC.

Keywords: ACC Publications, Cardiology Magazine, Acute Coronary Syndrome, Adenosine, Antibodies, Monoclonal, Anticoagulants, Aortic Valve, Aspirin, Atrial Fibrillation, Blood Pressure, Cardiac Catheterization, Cognition, Constriction, Pathologic, Coronary Stenosis, Coronary Vessels, Digoxin, Echocardiography, Stress, Echocardiography, Female, Fibrinolytic Agents, Heart Atria, Heart Defects, Congenital, Heart Valve Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipidemias, Hypertension, Ischemic Attack, Transient, Long-Term Care, Myocardial Infarction, Plaque, Atherosclerotic, Registries, Stroke, Thrombosis, Tomography, X-Ray Computed, Transcatheter Aortic Valve Replacement, Transcatheter Aortic Valve Replacement, Vasodilator Agents, Venous Thromboembolism, Venous Thrombosis, Warfarin, ACC Annual Scientific Session, ACC17