MIRACL trial

MIRACL) trial a new frontier for statins Curr Control Trials Cardiovasc Med 2001 2(3) lll-4. 

In the 80-mg simvastatin dose group in the Ato Z trial, CRP levels fell from 20,1 to 1,7 at four months and 1,5 at eight months (P < 0.001) (36). Higher-dose simvastatin resulted in lower CRP levels. In PROVE-IT (35), Ato Z (36), and MIRACL trials (37), higher doses of statin medications resulted in lower low-density cholesterol (LDL) and a better outlook. Higher doses of statin also caused greater falls in CRP levels. This suggests a role for inflammation in these ACS patients (37). 

Tsimikas S, Witztum JL, Miller ER et al. High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apohpoprotein B-lOO in patients with acute coronary syndromes in the MIRACL trial. 2004 110 1406-1412. 

MIRACLE trial MIRACLE-ICD trial Insync III trial Total... 

CRT also appears to confer long-term benefits on cardiac function. Several studies support a positive effect of CRT on cardiac remodeling. Yu et al. assessed CRT patients serially over 3 months. They found that there was progressive improvement in EF, LV end systolic volume, and LV end diastolic volumes (12). The MIRACLE trial similarly found progressive improvement of these parameters over 6 months of CRT patients (11). We frequently see patients continue to have symptomatic improvement several months after the procedure. 

The effects of CRT in mild heart failure have not been established. There have been two large-scale trials that included patients with NYHA functional class II heart failure—the CONTAK CD trial and the MIRACLE ICD trial [115, 116]. Although there was no consistent clinical benefit seen in either trial, both studies revealed evidence of reverse... 

Young JB, Abraham WT, Smith AL, et al. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure the MIRACLE ICD Trial, [see comment]. JAMA 2003 289 2685-94. 

Lenzer, Jeanne. Medicine s Magic Bullets Discover 29, no. 7 (July 2008) 46-52. Rather than produce miracle cures, prescription drugs are more likely, according to this article, to cause adverse reactions. The author describes problems ranging from biased clinical trials to excessive claims of benefits in advertising that lead to the widespread use of unsafe drugs and make clear the need for FDA reforms. 

The early clinical benefits observed in statin trials of acute coronary syndrome patients (MIRACL and PROVE-IT TIM 1-22) where coronary vascular inflammation, thrombosis, and unstable plaque are critical pathophysiologic elements that may be positively modified by statins compared to the more delayed benefits observed in statin trials of patients with stable coronary artery disease. 

Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes the MIRACL study a randomized controlled trial. JAMA 2001 285 171 I-171 8. 

Radium—that was the magic element which had brought Flannery and his gang of men into desolate Colorado to dig for carnotite. Almost twenty-five years before, this woman, with but one assistant, her beloved Pierre, had accomplished the miracle of Flannery s five hundred men backed by a great modern financial organization with every scientific invention at its disposal. She had accomplished this wonderful work in an abandoned old shed in Paris. She had solved a problem and blazed a trial that Flannery and others have since travelled with less travail. 

Beyond that, it would be little short of a miracle if the judges in the Federal Repubhc of Germany had not learned - from the way in which their Mannheim colleagues careers were abruptly cut short -that if they wish to keep their own jobs, they better convict Revisionists without mercy. My statement, that a point at issue for the judges in trials against Revisionists is always whose head it is that will roll that of the accused or that of the judge - a statement that was controversial in 1993182 - has thus been proven entirely correct only one year later. In practice it has even been taken a step further to save his own skin it does not suffice for the judge to merely convict the accused no, in addition he must also show the accused to be a monster, and must punish him as harshly as possible.183... 

In such trials as MUSTIC (7), PATH-CHF (8), MIRACLE (9), CONTAK CD (10), MIRACLE ICD (11), and PATH-CHF II (12), resynchronization therapy consistently improved functional capacity and reduced symptoms. Specifically, resynchronization was associated with a 1% to 23% improvement in 6-minute hall walk distance, a 7% to 10% increase in V02max, and an 11% to 31% improvement in quality of life scores. 

MUSTIC, PATH-CHF, MIRACLE, CONTAK CD, MIRACLE ICD, and PATH-CHF II enrolled patients with (a) moderate to severely symptomatic (NYHA class III—IV) CHF despite optimal medical therapy (b) severe left ventricular systolic dysfunction (LVEF <35%) (c) a wide QRS complex (generally defined as a QRS >120-130 msec) and (d) sinus rhythm. As a result, these inclusion criteria have become the standard indications for CRT. The effects in these conventional indication trials are robust—indeed, far more robust than the effects observed with conventional pharmacologic therapy of heart failure (Figure 5.1). For instance, improvement in 6-minute hall walk distance was observed in only 2 of 6 trials of ACE-inhibitors, 3 of 17 trials of beta blockers, and 1 of 4 trials of digoxin (13). Trials of both beta-blockers and ACE inhibitors have likewise shown inconsistent results with respect to V02max (14,15) and quality of life (16,17). 

In addition to improving symptoms, CRT has been demonstrated to improve survival in conventionally indicated populations. Although the early randomized clinical trials of CRT were not large enough to include mortality as a primary endpoint, a meta-analysis of MUSTIC, MIRACLE, MIRACLE ICD, and CONTAK CD concluded that resynchronization therapy, with or without concomitant use of a defibrillator, reduced mortality due to progressive heart failure by 51% (24). comparison of... 

Although resynchronization is proven to prolong survival compared with standard medical therapy of heart failure, it should be noted that there is no direct evidence that resynchronization therapy improves survival when compared with ICD therapy alone (24). It is also curious to note that the addition of resynchronization did not reduce ICD therapies for ventricular tachy-cardia/ventricular fibrillation in either the CONTAK CD or MIRACLE ICD trials (10,11). It is possible that these observations may reflect the relatively large proportion of secondary prevention patients enrolled in these trials (28), as well as the relatively short duration of follow-up. Indeed, a recent retrospective analysis of the InSync III Marquis trial showed that responders to CRT demonstrated significantly fewer single premature ventricular contractions beats, or PVC runs, and fewer treated episodes of ventricular tachycardia or fibrillation (VT/VF) (P = 0.050) than nonresponders by 6 months of follow-up (29). 

Conceptually, the potential complications of CRT-pacemaker or CRT-defibrillator implantation include the known complications of transvenous pacemaker or ICD implant (bleeding, infection, pneumothorax, vascular injury, cardiac perforation/tamponade, and cardiac decompensation from defibrillation testing) as well as the potential complications of LV lead implant (coronary venous dissection/perforation, contrast nephropathy, and perhaps elevated risk of infection or heart failure exacerbation due to prolonged procedure times). In addition, the passive fixation nature of LV leads raises the rates of post-procedure lead dislodgement. However, the rates of serious adverse events from the implantation procedure reported in the large clinical trials have been low. In MIRACLE, 2 patients (of 571) died as a result of the procedure. Correspondingly, 6% had a dissection or perforation of a coronary vein, but only 3 of those 35 patients required intervention and... 

Egoavil CA, Ho RT, Greenspon AJ, Pavri BB. Cardiac resynchronization therapy in patients with right bundle branch block analysis of pooled data from the MIRACLE and Contak CD trials. Heart Rhythm 2005 2 611—5. 

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