Cardiology Trials

NEJM 2003;348:1309-21. Background In patients with chronic systolic heart failure, aldosterone blockade reduced death and cardiovascular hospitalizations when added to an ACE inhibitor ( RALES trial), which will be reviewed in the section involving trials in patients with chronic heart failure. Efficacy of aldosterone blockade in patients with acute myocardial infarction, complicated by LV dysfunc...

NEJM 1995;333:1670-6. Background Up to this point in history, a series of trials had been conducted using ACEi’s in post-MI patients. A small to moderate short-term benefit had been shown when the drugs were started immediately ( GISSI-3 and ISIS-4 ) and much greater long-term benefits were demonstrated when the drugs were started 5-11 days, on average, following AMI in patients with LV dysfunctio...

Two important trials of beta-blockers in patients with acute myocardial infarction. See https://cardiologytrials.substack.com/ for full details. Get full access to Cardiology Trial’s Substack at cardiologytrials.substack.com/subscribe

Lancet 2005;366:1622-32 Background Beta blockers were routinely used for the early management of patients with AMI; however, their efficacy and safety remained uncertain in this clinical scenario. Recall that in the BHAT trial, propranolol reduced death 2 years following an AMI with an NNT of approximately 33 but the cohort was highly selected, the drug was started, on average, 14 days following a...

Lancet 2001;357:1385-90. Background While beta blockers were frequently used in patients with acute myocardial infarction complicated by heart failure, at the time the CAPRICORN trial was undertaken, supportive evidence from contemporary, large scale randomized trials was lacking. The BHAT and ISIS-1 trials, reviewed in this section, were published in 1982 and 1986, respectively; before contempora...

Two seminal trials of ACEi in patients with acute myocardial infarction complicated by heart failure or left ventricular systolic dysfunction. See https://cardiologytrials.substack.com for full details Get full access to Cardiology Trial’s Substack at cardiologytrials.substack.com/subscribe

Lancet 1993;342:821-28. Background The Survival After Ventricular Enlargement ( SAVE ) trial demonstrated that administration of the angiotensin converting enzyme inhibitor (ACEi) captopril, following MI complicated by LV dysfunction (EF ≤40%) but without clinical heart failure significantly improved morbidity and mortality over 3.5 years of follow-up. Yet many post-MI patients at the time had cli...

NEJM 1992;327:669-77 Background After a large heart attack, cardiac hemodynamics are altered, which leads to a series of changes in the heart muscle itself. The immediate consequence of a large heart attack is decreased myocardial contractility. This leads to a reduction in stroke volume and cardiac output. Compensatory mechanisms governed by the renin-angiotensin-aldosterone system and sympatheti...

Discussion of two landmark trials of ACEi and nitrates in acute coronary syndrome. ISIS-4 had also an arm for magnesium. The story of magnesium is very interesting!!! See https://cardiologytrials.substack.com/ for full details. Get full access to Cardiology Trial’s Substack at cardiologytrials.substack.com/subscribe

Lancet 1995;345:669-685. Background The premises for ISIS-4 were similar to GISSI-3 with the notable exception of adding an arm to test the effect of magnesium in acute myocardial infarction. Up to this point magnesium was commonly used in patients with acute MI. It was suspected to limit infarct size and reduce arrhythmic events and death; however, it was backed only by animal experiments and sma...

Lancet 1994;343:1115-22. Background By the time GISSI-3 was undertaken, evidence had emerged suggesting afterload reduction with angiotensin-converting-enzyme (ACE) inhibitors improved morbidity and mortality in patients with chronic systolic heart failure and these agents were already an established treatment for acute, severe heart failure based on theoretical grounds, despite lack of evidence f...

Discussion of the historic CAST and ISIS-3 trials. See https://cardiologytrials.substack.com/ for more details Get full access to Cardiology Trial’s Substack at cardiologytrials.substack.com/subscribe

Lancet 1992;339:753-770. Background Results from the GISSI and ISIS-2 trials demonstrated a clear benefit for the early opening of acutely blocked arteries with fibrinolytic treatment in patients presenting with STEMIs. ISIS-2 also demonstrated the benefit of aspirin in the acute and subacute phases of MI. However, after opening a blocked artery, concern for re-occlusion persisted, especially in t...

NEJM 1991;324:781-788 Background A hallmark of post-myocardial infarction (MI) care in the 1980’s was the monitoring and suppression of premature ventricular contractions (PVCs) via use of antiarrhythmic drugs. The practice was based on pathophysiologic rationale that PVC burden is a strong risk factor for sudden and non-sudden cardiac death following MI and thus, suppression must reduce death. PV...

A discussion of the historic trials of thrombolysis in myocardial infarction. See cardiologytrials.substack.com for more details. Get full access to Cardiology Trial’s Substack at cardiologytrials.substack.com/subscribe

Lancet 1990;336:65-71 . Background Large trials up to this point had established the role of thrombolytic therapy and aspirin in patients with acute MI. The next question centered on the different types of thrombolytic agents as well as the merits of adding high dose heparin to aspirin following revascularization. Data from smaller studies showed that alteplase (tPA) had a higher recanalization ra...

Lancet 1988;349-360 Background The introduction to the ISIS-2 manuscript opens with a remarkable statement from the authors: Reductions in mortality that are realistically moderate (eg, “only” 20-25%) are important, especially if produced by widely practicable treatments for common causes of death. At the time of this posting, January 2024, it’s amazing to think, how in 1988, a 20-25% reduction in...

Lancet 1986;397-401 Background This study by the Italian Group for the Study of Streptokinase in Myocardial Infarction ( GISSI ) is the first large trial to test the hypothesis that opening blocked heart arteries, in this case via use of the intravenous thrombolytic agent Streptokinase, reduces death in patients presenting with acute myocardial infarction (MI) . Opening blocked arteries or revascu...

An exploration of the pivotal BHAT and ISIS-I trials. Both of which significantly impacted physicians' use of beta-blockers in patients with acute myocardial infarction. However, there is still more to uncover! Get full access to Cardiology Trial’s Substack at cardiologytrials.substack.com/subscribe