2020 Mechanisms & Management of Cardiac Disorders


Papers and Guidelines

These are just a few studies and guidelines related to the content of the lectures. Many are landmark papers that have had lasting impact on the practice of cardiology.

Click on the trial name or image for the full paper.


General Principles in the Treatment of Acute Myocardial Infarction

ISIS-2 - 1988 - This trial randomized ~17,000 patients presenting with suspected acute MI (mostly STEMI) to daily aspirin vs placebo and to one-time IV streptokinase vs placebo. It found substantial and roughly equal benefit for both interventions. The lasting impact is that we give aspirin for acute MI. Thrombolytics like streptokinase still have a role, but have been mostly replaced by PCI.

TACTICS-TIMI 18 - 2001 - This trial randomized ~2000 patients presenting with NSTEMI to a conservative strategy (medical treatment, followed possibly by stress test) vs invasive strategy (coronary angiogram with the intent to revascularize within 48 hours). It found, on average, benefit to the invasive strategy. The lasting impact is that, for patients presenting to the hospital with a syndrome that is consistent with a type I NSTEMI (i.e. suspected plaque rupture) we favor initiating medical treatment immediately but proceeding to angiogram within a day or two.


Hypercholesterolemia and Vascular Disease

CTT Meta-analysis - 2010 - There are tons of randomized controlled trials for statins in both primary and secondary prevention. This meta-analysis combined ~170,000 patients from these trials. It found, on average across multiple indications, relative reductions of 22% for major vascular events, 14% for death from vascular causes, and 10% for all-cause mortality for each 1 mmol/L (or 38 mg/dL) of LDL reduction. Because these are relative reductions, absolute benefit will be greater for those at higher baseline risk. The lasting impact of the statin trials is that, for patients with established atherosclerotic cardiovascular disease, a high-dose statin is recommended, and for those without clinical disease but with a high calculated risk (at least 7.5% over 10 years), a statin is also recommended. The calculator can be found here.

Mitral Valve Disease

COAPT - 2018 - The most recent notable trial on intervention for mitral valve disease is this trial of 614 patients with mitral regurgitation secondary to heart failure with reduced systolic function. In secondary mitral regurgitation, the leaflets are usually tethered by papillary muscles that are overstretched due to the dilated LV, and the mitral annulus can enlarge as well. This trial randomized patients with moderate-severe or severe secondary regurgitation to usual therapy for heart failure vs usual therapy plus a clip, placed with a transcatheter method, that pinches the middle of the two mitral leaflets together to create a tissue bridge and a resulting valve with two smaller orifices. It is important to note that another trial, MITRA-FR had a similar design but failed to show benefit, perhaps because of different participant characteristics. The lasting impact of COAPT remains to be seen, but overall it will likely mean that patients with secondary mitral regurgitation with HFrEF should at least be considered for mitral valve clip therapy if there remains severe MR and LV dysfunction despite all the other established HF therapy.

Antiplatelet and Anticoagulant Therapy for CAD

See ISIS-2 above for aspirin in acute MI.

CURE - 2001 - This trial randomized 12,500 patients with NSTEMI—all being treated with aspirin—to placebo vs clopidogrel, the platelet ADP receptor (also known as P2Y12) inhibitor. The composite of cardiovascular death, myocardial infarction, and stroke was less frequent in those getting clopidogrel. The lasting impact is that, in addition to aspirin, we give clopidogrel (or the other P2Y12 inhibitors ticagrelor or prasugrel based on later trials) for acute MI.

Non-invasive Evaluation of Coronary Artery Disease

PROMISE - 2015 - This trial randomized 10,000 outpatients who presented with a symptom concerning for angina to either a functional stress test (exercise or pharmacologic with EKG, nuclear perfusion imaging, or echocardiogram as the readout) vs an anatomic CT angiogram of the coronary arteries. Whatever happened afterwards (i.e. proceed to cardiac catheterization and possible revascularization, or focus on medical management, or look for non-cardiac causes of the symptom) was not dictated by the trial and essentially up to the treating physicians. It found no difference in outcomes between the two initial testing strategies. The impact is that, as initial evaluation for someone without known CAD, either a functional (stress) or anatomical (CT angiogram) test is a reasonable non-invasive choice.

Hypertension

SPRINT - 2015 - This trial randomized ~10,000 patients with hypertension and increased CV risk, but without diabetes, to a traditional SBP goal of 140 vs an intensive SBP goal of 120 mm Hg. It found less frequent combined myocardial infarction, stroke, heart failure, or cardiovascular death in the intensive arm. The lasting impact is that in patients with CVD or calculated CV risk of 10% or higher, a BP target of less than 130/80 mm Hg is recommended, and for everyone else would be reasonable.

Pulmonary Embolism

PEITHO - 2014 - High risk, hemodynamically unstable PEs should generally receive thrombolytic therapy in addition to heparin. Low risk PEs should receive anticoagulation alone. This trial randomized ~1000 patients with intermediate risk PEs (stable but with signs of RV strain either on imaging or by troponin) and looked at 7-day outcomes. It found thrombolytic therapy was associated with reduced hemodynamic decompensation but increased major hemorrhage and stroke. The lasting impact is that in patients with intermediate risk PE, we are still trying to define the ideal patients for thrombolysis and often choosing a catheter-directed approach in order to minimize systemic therapy, although this strategy would benefit from more evidence that it helps hard outcomes.


Heart Failure and Kidney Disease

Dr. Bakris has provided this paper to supplement his lecture: HF and Kidney Disease - 2019

Heart Failure with Reduced Ejection Fraction (HFrEF)

PARADIGM - 2014 - This trial randomized ~8000 patients with symptomatic HFrEF and elevated BNP to sacubitril-valsartan (Angiotensin Receptor-Neprilysin Inhibitor, or ARNI) vs enalapril (ACE inhibitor). It found that sacubitril-valsartan was associated with less combined death and heart failure hospitalization than enalapril. The lasting impact is that ARNI therapy is now part of class I recommendations for HFrEF as an alternative to ACE inihbitors or angiotensin receptor blockers (ARB), and for patients with HFrEF already on an ACE inhibitor or ARB but still symptomatic, replacement by an ARNI should be considered.

Implantable Electronic Devices

SCD-HeFT - 2005 - This trial randomized ~2500 symptomatic patients with HFrEF (LVEF <= 35%) to placebo vs amiodarone vs ICD to determine if one or the other was superior in reducing death from any cause (with the idea to reduce sudden death from VT/VF as a primary prevention strategy). It found no benefit for amiodarone but ICD was associated with less death (HR = 0.77). The lasting impact of this trial, in combination with a few other trials on primary prevention ICDs, is that for most patients with symptomatic HFrEF and LVEF < = 35%, ICD is recommended for primary prevention. We usually give patients a chance to recover LVEF with medical therapy and revascularization (if ischemic) before deciding that it is time for the ICD.