Faculty Bibliography

BACKGROUND: Contemporary studies have shown that spontaneous but not procedural myocardial infarction (MI) are related to subsequent mortality. Whether PCI reduces spontaneous (non-procedural) MI is unknown. METHODS AND RESULTS: PUBMED, EMBASE, and CENTRAL were searched for randomized clinical trials (RCTs), until October 2012, comparing PCI with OMT, for stable ischemic heart disease, and reporting MI outcomes - spontaneous non-procedural MI, procedural MI and all MI including procedure related MI. Given the varying length of follow-up between trials, a mixed-effect poisson regression meta-analysis was employed. From 12 RCTs with 37548 patient-years of follow-up, PCI, when compared with OMT alone, was associated with significant lower incident rate ratio (IRR) for spontaneous non-procedural MI (IRR=0.76, 95% CI 0.58-0.99) at the risk of higher procedural MI (IRR=4.11, 95% CI 2.53-6.88) without any difference in all MI (IRR=0.96, 95% CI 0.74-1.21). The point estimate for PCI vs. OMT for all-cause mortality (IRR=0.88, 95% CI 0.75-1.03) and cardiovascular mortality (IRR=0.70, 95% CI 0.44-1.09) paralleled that of spontaneous non-procedural MI (but not procedural or all nonfatal MI) although these were not statistically significant. CONCLUSIONS: PCI compared to OMT reduced spontaneous MI at the risk of procedural MI without any difference in all MI. Consistent with prior studies showing that spontaneous MI but not procedural MI are related to subsequent mortality, in the present report the point estimate for reduced mortality with PCI compared to OMT paralleled the prevention of spontaneous MI with PCI. Further studies are needed to determine whether these associations are causal.

In patients on conventional heart failure therapy including angiotensin-converting enzyme (ACE) inhibitors, the addition of angiotensin receptor blockers (ARBs), direct renin inhibitors (DRIs), or aldosterone antagonists are therapeutic options to further reduce the risk of cardiovascular events. However, whether one is preferable over the other is not known. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for randomized clinical trials (RCTs), until March 2011, of trials testing either an ARB, DRI, or an aldosterone antagonist in patients with heart failure who were on conventional heart failure therapy with follow-up of at least 3 months. Efficacy (death, cardiovascular death, nonfatal myocardial infarction, heart failure hospitalization and composite of cardiovascular death or heart failure hospitalization) and safety (hyperkalemia, hypotension, renal failure) outcomes were compared. The authors identified 16 RCTs involving 31,429 participants that satisfied the inclusion criteria. When compared with placebo (reference rate ratio [RR] of 1), aldosterone antagonists reduced the rate of death (RR, 0.79; 95% credibility interval [CrI], 0.66-0.98), cardiovascular death (RR, 0.78; 95% CrI, 0.65-0.93), heart failure hospitalization (RR, 0.74; 95% CrI, 0.55-0.94), and the composite of cardiovascular death or heart failure hospitalization (RR, 0.73; 95% CrI, 0.55-0.90) with no difference for other efficacy outcomes. However, ARBs and DRIs did not result in any significant reduction in the rate of any of the efficacy outcomes when compared with placebo. When compared with placebo (RR=1), ARBs increased the rate of hyperkalemia (138% increase), renal failure (126% increase), and hypotension (63% increase). Similarly, aldosterone antagonists resulted in a 110% increase in hyperkalemia and DRIs with a 98% increase in hypotension. In patients with heart failure and reduced systolic function on conventional heart failure medications, the risk benefit ratio favors the addition of aldosterone antagonists over ARBs or DRIs.

BACKGROUND: Intravenous (IV) beta-blockade is currently a Class IIa recommendation in early management of patients with acute coronary syndromes (ACS) without obvious contraindications. METHODS: We searched the PubMed, EMBASE and the Cochrane Register for Controlled Clinical Trials for randomized clinical trials from 1965 through December, 2011, comparing intravenous beta-blockers administered within 12hours of presentation of ACS with standard medical therapy and/or placebo. The primary outcome assessed was the risk of short-term (in-hospital mortality-with maximum follow up duration of 90days) all-cause mortality in the intervention group versus the comparator group. The secondary outcomes assessed were ventricular tachyarrhythmias, myocardial reinfarction, cardiogenic shock, and stroke. Pooled treatment effects were estimated using relative risk with Mantel-Haenszel risk ratio, using a random-effects model. RESULTS: Sixteen studies enrolling 73,396 participants met the inclusion exclusion criteria. In- hospital mortality was reduced 8% with intravenous beta-blockers, RR=0.92 (95% CI, 0.86-1.00; p=0.04) when compared with controls. Moreover, intravenous beta-blockade reduced the risk of ventricular tachyarrhythmias (RR=0.61; 95 % CI 0.47-0.79; p=0.0003) and myocardial reinfarction (RR=0.73, 95 % CI 0.59-0.91; p=0.004) without increase in the risk of cardiogenic shock, (RR=1.02; 95% CI 0.77-1.35; p=0.91) or stroke (RR=0.58; 95 % CI 0.17-1.98; p=0.38). CONCLUSIONS: Intravenous beta-blockers early in the course of appropriate patients with ACS appears to be associated with significant reduction in the risk of short-term cardiovascular outcomes, including a reduction in the risk of all-cause mortality.

CONTEXT: Most guidelines for treatment of hypertension including the Joint National Committee-7 recommend a blood pressure (BP) goal of <140/90 mm Hg for hypertensive patients and a more aggressive goal of <130/80 mm Hg for patients with coronary artery disease (CAD), based largely on expert consensus. OBJECTIVE: To evaluate the BP targets in patients with CAD DATA SOURCES: PUBMED, EMBASE and CENTRAL Study Selection: Randomised clinical trials (RCTs) of antihypertensive therapy in patients with CAD, enrolling at least 100 patients, with achieved systolic pressure of <=135 mm Hg in the 'intensive BP' group and <=140 mm Hg in the 'standard BP' group with follow-up for at least 1 year and evaluating cardiovascular outcomes. DATA EXTRACTION: The following efficacy outcomes were extracted- all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, heart failure and revascularisation. RESULTS: We identified 15 RCTs enrolling 66 504 participants with 276 328 patient-years of follow-up. Intensive BP group (