Year : 2017 | Volume
: 3 | Issue : 1 | Page : 18--21
Cardiology update 2017: The first quarter
Department of Cardiology, AIIMS, New Delhi, India
Department of Cardiology, AIIMS, New Delhi
In the first quarter of 2017, proprotein convertase subtilisin/kexin type 9's role got defined further with a number of trials such as FOURIER, ORION-1, and SPIRE 1 and 2. TAVI proves safe in intermediate-risk patients in the Surgical Replacement and Transcatheter Aortic Valve Implantation study. Newer anticoagulants extended their role to valvular heart disease. Bioabsorbable stent showed problems (ABSORB 2 and 3). New guidelines have been released for syncope and transcatheter aortic valve replacement implantation. Clinical outcome studies involving instantaneous wave-free ratio (IFR) showed IFR to be noninferior to fractional flow reserve. Optimal medical therapy proves noninferior to percutaneous coronary intervention in single vessel chronic total occlusion.
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Umapathy S. Cardiology update 2017: The first quarter.J Pract Cardiovasc Sci 2017;3:18-21
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Umapathy S. Cardiology update 2017: The first quarter. J Pract Cardiovasc Sci [serial online] 2017 [cited 2021 Jun 18 ];3:18-21
Available from: https://www.j-pcs.org/text.asp?2017/3/1/18/210859
The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab decreased major cardiovascular (CV) events risk, according to results from the long-anticipated outcomes trial Further CV Outcomes Research with PCSK9 inhibition in subjects with elevated risk (FOURIER) and significantly lowered low-density lipoprotein (LDL) levels. The study which included participants with CV disease (CVD) receiving statins showed evolocumab at doses of 140 mg every other week or 420 mg monthly had a 15% reduced risk for the composite of myocardial infarction (MI), stroke, CV death, coronary revascularization, and unstable angina hospitalization at 22 months compared with those receiving matching placebo (P< 0.001). In summary, there is a 2% mortality benefit on the drug in LDL-resistant patients who have had a prior heart attack or stroke or peripheral vascular disease. The drug now needs to prove its value, i.e. efficacy combined with cost to establish its role in the market.
Inclisiran suppresses PCSK9 synthesis in the liver and can lower levels of LDL cholesterol and may be useful for injection every 6 months as shown in the ORION-1 study.
ORION-1 is a double-blind, placebo-controlled trial of inclisiran administered by subcutaneous injection in adults with high LDL-C and at high risk of CVD. LDL-C (LDL-cholesterol) levels had to be above 70 mg/dL or 100 mg/dL for those with or without a history of atherosclerotic CVD, respectively. Patients received placebo or inclisiran and most participants (73%) were receiving statins and 31% were receiving ezetimibe at study entry. For the primary end point, the mean reduction from baseline of LDL-C at day 180 was 27.9% to 41.9% after a single dose of inclisiran, compared with a 2.1% increase for placebo. The optimal dose was 300 mg given twice at 6-month dosing interval. All patients appeared to respond, and at 6 months, the mean reduction in LDL-C was 52.6%, with a maximum response of almost 81%.
The Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) trial showed that the transcatheter aortic valve replacement (TAVR) is comparable to surgery in severe aortic stenosis patients deemed intermediate risk.
Clinical data from the SURTAVI trial, was presented at the American College of Cardiology (ACC) 66th Annual Scientific Session and published simultaneously in the New England Journal of Medicine.
Data from the trial showed the Medtronic self-expanding TAVR platform met its primary endpoint of all-cause mortality or disabling stroke at 2 years. The rates of all-cause mortality or disabling stroke at 2 years were similar to surgical aortic valve replacement (SAVR). TAVR also demonstrated better mean aortic valve gradient at 2 years, while neither TAVR- nor SAVR-treated patients displayed evidence of valve deterioration at 2 years.
The PCSK9 inhibitor bococizumab outcome trials SPIRE 1 and 2 showed that antidrug antibodies developed in a large proportion of patients and significantly attenuated the LDL-lowering effect.,
The results of the trials with bococizumab and SPIRE 1 and 2 show that antidrug antibodies developed in a large proportion of patients and significantly attenuated the LDL-lowering effect.
The SPIRE 1 and 2 studies were stopped because of the immunogenicity issues with the drug. Bococizumab in SPIRE 2 reduced CV events in patients with higher LDL levels at baseline (>100 mg/dL) who were followed for a longer duration (median 12 months). However, the drug had no effect on CV events in SPIRE 1 which included patients with lower LDL levels at baseline (>70 mg/dL) who were followed for a shorter duration (median 7 months).
In the bococizumab program, antidrug antibodies developed in almost half (48%) of the patients who received bococizumab and neutralizing antibodies developed in 29%. This substantially attenuated LDL lowering over time in some patients. There was wide variability in the LDL lowering achieved with bococizumab even among patients who did not develop antibodies.
In patients with venous thromboembolism (VTE) who had completed 6–12 months of anticoagulation therapy, but for whom it was uncertain as to whether long-term treatment was needed, extended therapy with rivaroxaban, at either 20 mg or 10 mg was more effective than aspirin at preventing recurrent VTE without an increased risk of bleeding in the EINSTEIN CHOICE trial.
“Newer anticoagulants (NOACs), and in particular edoxaban, are safe and effective in patients with most all types of patients with valvular heart disease (VHD) (except for mechanical valves and mitral stenosis [MS]),”
The first of the studies reported online March 21, by Caterinaet al., compares patients on edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial. The second is a systematic review and meta-analysis of comparative trials of NOACs versus vitamin K antagonists. Both papers appear in the Journal of the ACC.
The Food and Drug Administration is investigating the significant increase in major adverse cardiac events (MACEs) seen for the everolimus-eluting bioresorbable vascular scaffold versus everolimus-eluting metal stent in a 2-year data from the ABSORB 3 trial.
The trial saw an 11% increase in the composite of cardiac death, MI, or repeat revascularization over 2 years in patients who received the Absorb stent versus Xience.
This is more in the smaller-caliber Absorb scaffolds, which have not been recommended.
In patients with coronary artery disease and statins, no differences were seen between patients receiving evolocumab and placebo with various cognitive tests between the beginning and end of the study, in either treatment group in the EBBINGHAUS study.
The European Commission has approved an update to the sodium-glucose cotransporter-2 inhibitor empagliflozin status and it is now indicated for poorly controlled diabetes. Empagliflozin is the only oral diabetes treatment shown to reduce the risk of CV death in a trial. The EMPA-REG OUTCOME trial showed that empagliflozin reduced the risk of CV death by 38% versus placebo in patients with diabetes mellitus and established CV disease when added to standard of care.
A 2017 ACC expert consensus provides practical guidelines about TAVR, including point-of-care checklists and algorithms regarding preprocedure evaluation of the patient, imaging modalities and measurements, key issues in performing the TAVR procedure, and recommendations for patient follow-up.
Another 2017 ACC guideline discusses the management of adult and pediatric patients suspected to have syncope. Risk stratification and prevention of sudden cardiac death in selected populations are also discussed. This guideline identifies areas in which to foster collaborative efforts to improve understanding of syncope. It covers in detail syncope as related to various causes such as ischemic heart disease, cardiomyopathies, inheritable causes, and reflex conditions such as vasovagal syncope and orthostatic hypotension.
In recent ACC/American Heart Association (AHA) VHD guidelines 2017, TAVR was given Class I indication in patients with severe aortic stenosis who have high-surgical risk and in those with prohibitive surgical risk. Similarly, TAVR is considered as a reasonable alternative (Class IIa indication) in those with intermediate surgical risk due to the recent SURTAVI trial.
Valvular atrial fibrillation (AF) except rheumatic MS, CHA2DS2Vasc score to be utilized to decide for antithrombotic therapy. NOACs can be used as an alternative to warfarin (Class IIa) in valvular AF except rheumatic MS.
Mitral valve (MV) surgery is reasonable in asymptomatic severe primary mitral regurgitation (MR) with preserved left ventricular ejection fraction (LVEF) and left ventricular end-systolic diameter <40 mm (Stage C1) who show a progressive increase in left ventricular (LV) size or decrease in LVEF on serial imaging (Class II).
MV replacement is preferred over MV repair in chronic, severe ischemic MR with persistent symptoms despite guideline-directed medical therapy. The recommended definition of severe secondary MR is now the same as for primary MR (effective regurgitant orifice ≥0.4 cm2 and regurgitant volume ≥60 ml).
Age limit for favoring mechanical heart valves reduced to 50 years from 60 years. Patients with transcatheter prosthetic valves and annuloplasty rings and chords also to be given infective endocarditis prophylaxis.
The CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) investigated the impact of infusing an engineered, prebeta high-density lipoprotein (HDL) mimetic containing sphingomyelin, and dipalmitoyl phosphatidylglycerol (CER-001) on coronary atheroma volume in patients with a recent acute coronary syndrome (ACS).
The CARAT was a Phase 2, multicenter trial in which patients with an ACS undergoing intracoronary ultrasonography and showing percent atheroma volume (PAV) greater than 30% were randomly assigned to treatment with ten infusions of CER-001 or matching placebo, administered at weekly intervals.
There was no significant difference in the primary endpoint, which was the PAV as measured by intravascular ultrasound. There were also no significant differences in LDL, HDL, triglycerides, and high-sensitivity C-reactive protein.
In the Decision CTO trial, optimal medical therapy (OMT) as an initial strategy was non-inferior to percutaneous coronary intervention (PCI) in patients with coronary chronic total occlusion (single vessel CTO) with respect to the primary endpoint of the composite of death, MI, stroke, or any revascularization at 3-year follow-up.
The goal of the trial was to assess the safety and efficacy of CTO PCI compared with OMT among patients with at least one CTO. The results indicate that routine CTO-PCI + OMT is not superior to OMT alone in reducing CV outcomes among patients with at least one CTO. EXPLORE was another CTO-PCI trial recently published that focused on patients with STEMI undergoing primary PCI with a coexistent CTO and showed no improvement in LV function with CTO-PCI.
Instantaneous Wave-Free Ratio (iFR) is a resting physiological index used to assess the functional significance of coronary artery stenosis. In recent two large clinical outcome studies involving more than 2000 subjects in each study, iFR-guided coronary revascularization was proven non-inferior to fractional flow reserve (FFR)-guided strategy with respect to MACEs at 12 months with shorter procedural time.,
In compare-ACUTE trial involving 885 patients, FFR-guided revascularization of a noninfarct artery in ST-elevation myocardial infarction patients who underwent primary PCI of the infarct-related artery resulted in a lower risk of composite CV outcomes mainly by a reduction in subsequent revascularizations.
In EUCLID trial involving 13,885 patients with symptomatic PAD, ticagrelor was not shown to be superior to clopidogrel with respect to reduction of CV events and at similar bleeding risk.
The presence of implantable CV electronic devices has been long considered a contraindication for doing magnetic resonance imaging (MRI). In a recent prospective registry-based study, it had been shown that patients with non-MRI compatible pacemaker or implantable cardioverter defibrillator can undergo non-thoracic MRI at 1.5 tesla safely if appropriately screened and reprogrammed preprocedure.
In ENDURANCE trial involving patients with advance heart failure, smaller intrapericardial centrifugal flow left ventricular assist device (LVAD) (HeartWare) was found to be noninferior to axial flow LVAD (Heart-Mate II) as destination therapy with respect to device failure or stroke at 2 years.
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Conflicts of interest
There are no conflicts of interest.
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