Faculty Bibliography

OPINION STATEMENT: Coronary artery disease is the leading cause of death and disability worldwide. While an invasive strategy of early revascularization reduces cardiovascular morbidity and mortality in patients with acute coronary syndromes, there is no convincing evidence that this strategy leads to an incremental survival advantage for patients with stable ischemic heart disease (SIHD) beyond that achieved by optimal medical therapy. Two landmark trials, COURAGE and BARI 2D, suggest that a strategy of aggressive medical therapy is a reasonable initial approach to such patients. However, there remain certain groups of patients, those with at least moderate ischemia on baseline stress testing, where there is still clinical equipoise. Major society guidelines favor revascularization based on observational data and trials of CABG conducted decades ago, yet data from modern randomized trials are lacking. Ongoing trials such as ISCHEMIA should provide clinicians with evidence to guide selection of the appropriate initial management strategy for patients with SIHD.

BACKGROUND Dual calcium-channel blocker (CCB) with a dihydropyridine (DHP) and a nondihydropyridine (NDHP) has been proposed for hypertension treatment. However, the safety and efficacy of this approach is not well known. METHODS A MEDLINE/EMBASE/CENTRAL search for randomized clinical trials published on this topic from 1966 to February 2012 was performed. Efficacy outcomes of decrease in systolic (SBP) and diastolic (DBP) blood pressures from baseline, changes in heart rate (HR), and adverse effects were compared between dual CCB therapy vs. DHP or NDHP. SBP, DBP, and HR were expressed as weighted mean deviation (WMD). RESULTS A total of 6 studies with 153 patients were included. Dual CCB produced a significantly greater reduction in SBP (21.6+/-9.2 mmHg) from baseline than DHP (10.3+/-6.3 mmHg (WMD = 10.9 mmHg, P < 0.0001)) or NDHP (8.9+/-4.2 mmHg (WMD = 14.1 mmHg, P = 0.002)). Dual CCB therapy reduced DBP from baseline more than either monotherapy (dual CCB = 17.5+/-10.2 mmHg vs. DHP = 11.6+/-8.7 mmHg, WMD = 5.5 mmHg, P < 0.001; and NDHP = 10.5+/-5.6 mmHg, WMD = 5.3 mmHg, P = 0.03). Dual CCB therapy had significantly lower HR compared to DHP (P < 0.001) but was comparable to NDHP (P = 0.12) (Delta change dual CCB = -4.0+/-3.5 vs. DHP = -2.0+/-1.5 and NDHP = -6.0+/-5.0 beats/min). Dual CCB therapy did not increase adverse effects. CONCLUSIONS Dual CCB therapy lowers blood pressure significantly better than CCB monotherapy, without an increase in adverse events. However, given the lack of long-term outcome data on efficacy and safety, dual CCB therapy should be used with restraint, if at all. Large-scale long-term trials are needed to further evaluate such a strategy.

OBJECTIVE: To compare the long term efficacy and adverse events of dual blockade of the renin-angiotensin system with monotherapy. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, and the Cochrane central register of controlled trials, January 1990 to August 2012. STUDY SELECTION: Randomised controlled trials comparing dual blockers of the renin-angiotensin system with monotherapy, reporting data on either long term efficacy (>/=1 year) or safety events (>/=4 weeks), and with a sample size of at least 50. Analysis was stratified by trials with patients with heart failure versus patients without heart failure. RESULTS: 33 randomised controlled trials with 68 405 patients (mean age 61 years, 71% men) and mean duration of 52 weeks were included. Dual blockade of the renin-angiotensin system was not associated with any significant benefit for all cause mortality (relative risk 0.97, 95% confidence interval 0.89 to 1.06) and cardiovascular mortality (0.96, 0.88 to 1.05) compared with monotherapy. Compared with monotherapy, dual therapy was associated with an 18% reduction in admissions to hospital for heart failure (0.82, 0.74 to 0.92). However, compared with monotherapy, dual therapy was associated with a 55% increase in the risk of hyperkalaemia (P<0.001), a 66% increase in the risk of hypotension (P<0.001), a 41% increase in the risk of renal failure (P=0.01), and a 27% increase in the risk of withdrawal owing to adverse events (P<0.001). Efficacy and safety results were consistent in cohorts with and without heart failure when dual therapy was compared with monotherapy except for all cause mortality, which was higher in the cohort without heart failure (P=0.04 v P=0.15), and renal failure was significantly higher in the cohort with heart failure (P<0.001 v P=0.79). CONCLUSION: Although dual blockade of the renin-angiotensin system may have seemingly beneficial effects on certain surrogate endpoints, it failed to reduce mortality and was associated with an excessive risk of adverse events such as hyperkalaemia, hypotension, and renal failure compared with monotherapy. The risk to benefit ratio argues against the use of dual therapy.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is the standard of care in acute coronary syndromes. Additionally, novel P2Y12 receptor antagonists such as prasugrel and ticagrelor are even recommended over clopidogrel in certain clinical guidelines. Despite the fact that clopidogrel is fraught with significant variability in on-treatment platelet reactivity, the novel P2Y12 receptor antagonists come at the price of increased side effects and cost. Therefore, alternative or supplementary antiplatelet therapies are needed. Cilostazol, a phosphodiesterase III inhibitor, has been shown to significantly improve high on-treatment platelet reactivity in patients receiving both aspirin and clopidogrel and has antiproliferative effects (inhibiting neointimal hyperplasia and smooth muscle proliferation), thus reducing the risk of restenosis after coronary stent implantation. Further, cilostazol in addition to aspirin and clopidogrel versus DAPT in patients undergoing percutaneous coronary intervention showed that triple antiplatelet therapy (TAPT) was associated with a significantly greater platelet inhibition, reduced major adverse cardiovascular events, target lesion revascularization, and target vessel revascularization with no increased risk for a hemorrhagic event. Moving forward, larger randomized controlled trials are required comparing TAPT versus DAPT (clopidogrel, prasugrel or ticagrelor on top of aspirin). (c) 2013 S. Karger AG, Basel.

BACKGROUND: Amiodarone use has been rarely associated with the development of acute respiratory distress syndrome (ARDS), usually in association with surgery or pulmonary angiography. In patients with preexisting left ventricular dysfunction, the diagnosis may be overlooked. CASE REPORT: A 92-year-old woman with a history of atrial fibrillation who was on low-dose amiodarone presented to the Emergency Department with sudden onset of shortness of breath. The patient was started on treatment for acute heart failure based on the physical examination and the elevated brain natriuretic peptide level. Despite adequate diuresis, the patient showed no improvement. A chest computed tomography scan revealed acute interstitial pneumonitis. The patient received corticosteroids due to suspected amiodarone-induced acute interstitial pneumonitis resulting in ARDS. She returned to her baseline activity within 2 weeks of the therapy. CONCLUSION: Although rare, clinicians should be vigilant for amiodarone-induced acute interstitial pneumonitis resulting in ARDS, as delay in treatment may result in a high risk of mortality. In addition, the development of ARDS occurred in our patient in the absence of precipitating factors such as surgery or pulmonary angiography

Drug-eluting stents have dramatically reduced the risk of restenosis, but concerns of an increased risk of stent thrombosis have provided uncertainty about their use. Recent studies have continued to show improved procedural and clinical outcomes with drug-eluting stents both in the setting of acute coronary syndromes and stable coronary artery disease. Newer generation drug-eluting stents (especially everolimus-eluting stents) have been shown to be not only efficacious but also safe with reduced risk of stent thrombosis when compared with bare-metal stents, potentially changing the benchmark for stent safety from bare-metal stents to everolimus-eluting stents. While much progress is being made in the development of bioabsorbable polymer stents, nonpolymer stents and bioabsorbable stent technology, it remains to be seen whether these stents will have superior safety and efficacy outcomes compared with the already much improved rates of revascularization and stent thrombosis seen with newer generation stents (everolimus-eluting stents and resolute zotarolimus-eluting stents).