Faculty Bibliography

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.

BACKGROUND: The efficacy and safety of drug-eluting stents (DES) in patients with ST-segment-elevation myocardial infarction (STEMI) is controversial. Consequently, DES implantation has a class IIa indication in the American College of Cardiology/American Heart Association and the European Society of Cardiology STEMI guidelines. METHODS AND RESULTS: PUBMED, EMBASE, and CENTRAL were searched for randomized clinical trials, until March 2013, comparing any of the 5 Food and Drug Administration-approved durable stent and polymer DES (sirolimus eluting stent, paclitaxel eluting stent, everolimus-eluting stent [EES], zotarolimus-eluting stent, and zotarolimus-eluting stent resolute), against each other or bare metal stents (BMS), and enrolling >/=50 patients with STEMI. Efficacy (target vessel revascularization) and safety (death, myocardial infarction, and stent thrombosis) outcomes at the longest reported follow-up times were evaluated. Twenty-eight randomized clinical trials with 34 068 patient-years of follow-up on subjects with STEMI fulfilled the inclusion criteria. When compared with BMS (reference rate ratio [RR] of 1), sirolimus eluting stent (RR, 0.46; 95% credibility interval [CrI], 0.36-0.56), paclitaxel eluting stent (RR, 0.69; 95% CrI, 0.53-0.87), and EES (RR, 0.42; 95% CrI, 0.26-0.62) were associated with a statistically significant reduction in rate of target vessel revascularization, with the point estimate for zotarolimus-eluting stent resolute trending in a similar direction. There was no increase in the risk of death, myocardial infarction, or stent thrombosis with any DES compared with BMS. Moreover, EES was associated with a statistically significant reduction in the rate of stent thrombosis when compared with sirolimus eluting stent (RR, 0.38; 95% CrI, 0.21-0.74), paclitaxel eluting stent (RR, 0.39; 95% CrI, 0.21-0.73), and even BMS (RR, 0.42; 95% CrI, 0.23-0.76). There was a 74% probability that EES had the lowest rate of any stent thrombosis when compared with all other stent types (no data on zotarolimus-eluting stent resolute). There was no increase in very late stent thrombosis with EES versus BMS (RR, 0.89; 95% CrI, 0.09-8.67). CONCLUSIONS: In patients with STEMI, DES versus BMS was associated with substantial decrease in the risk of target vessel revascularization without compromising safety. EES had the added advantage of substantial reduction in the risk of stent thrombosis when compared with first-generation DES and BMS with no increase in very late stent thrombosis.

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.

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 (