Faculty Bibliography

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the pathogenesis of hypertension (HTN). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are first line anti-HTN drug classes that are potent, effective and largely safe. Direct renin inhibitors (DRIs) have shown similar blood pressure (BP) reduction but more side effects. The efficacy of ACEIs and ARBs (for cardiovascular, cerebrovascular and renal protection) has been promoted to extend beyond what could be explained by BP reduction alone. In the current review, we will briefly discuss theBromfield and Muntner (Jun 2013) pathophysiology of renin-angiotensin-aldosterone system (RAAS) system,World Health Organization. A Global Brief on Hypertension: Silent Killer, Global Public Health Crisis (April 2013) clinical evidence for ACEIs, ARBs and DRIs in HTN,Bian et al. (Nov-Dec 2010) comparison of ACEIs vs ARBs and combination therapy,Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N. Engl. J. Med. Jan 20 (2000) role of RAAS inhibitors in specific patient populations,Group PC. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. Sep 29 (2001) safety profile of RAAS inhibitors, andPitt B, O'Neill B, Feldman R, et al. The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. Am. J. Cardiol. May 1 (2001) guideline recommendations and future perspectives. Closer scrutiny of outcome data shows little, if any, evidence that the efficacy of RAAS blockers in HTN extends beyond BP reduction.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to surgical aortic-valve replacement (SAVR) for patients with severe symptomatic aortic stenosis (AS) who are at high operative risk. We sought to determine the long-term (>/=1year follow-up) safety and efficacy TAVR compared with SAVR in patients with severe AS. METHODS: A comprehensive search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and relevant Web sites from inception through 10 April 2016. RESULTS: Fifty studies enrolling 44,247 patients met the inclusion criteria. The mean duration follow-up was 21.4months. No difference was found in long-term all-cause mortality (risk ratios (RR), 1.06; 95% confidence interval (CI) 0.91-1.22). There was a significant difference favoring TAVR in the incidence of stroke (RR, 0.82; 95% CI 0.71-0.94), atrial fibrillation (RR, 0.43; 95% CI 0.33-0.54), acute kidney injury (RR, 0.70; 95% CI 0.53-0.92), and major bleeding (RR, 0.57; 95% CI 0.40-0.81). TAVR had significant higher incidence of vascular complications (RR, 2.90; 95% CI 1.87-4.49), aortic regurgitation (RR, 7.00; 95% CI 5.27-9.30), and pacemaker implantation (PPM) (RR, 2.02; 95% CI 1.51-2.68). TAVR demonstrated significantly lower stroke risk compared to SAVR in high-risk patients (RR, 1.49; 95% CI 1.06-2.10); no differences in PPM implantation were observed in intermediate-risk patients (RR, 1.68; 95% CI 0.94-3.00). In a meta-regression analysis, the effect of TAVR baseline clinical features did not affect the long-term all-cause mortality outcome. CONCLUSION: TAVR and SAVR showed similar long-term survival in patients with severe AS; with important differences in treatment-associated morbidity.

The comparative efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) with other agents in patients >/=65 years of age with cardiovascular diseases or at-risk are unknown. Electronic databases were systematically searched to identify all randomized controlled trials that compared ACEIs with control (placebo or active) and reported long-term cardiovascular outcomes. We required the mean age of patients in the studies to be >/=65 years. Random-effects model was used to pool study results. Sixteen trials with 104,321 patients and a mean follow-up of 2.9 years were included. Compared with placebo, ACEIs significantly reduced all outcomes except stroke. Compared with active controls, ACEIs had similar effect on all-cause mortality (relative risk [RR] 0.99, 95% confidence interval [CI] 0.95 to 1.03), cardiovascular mortality (RR 0.99, 95% CI 0.93 to 1.04), heart failure (RR 0.97, 95% CI 0.91 to 1.03), myocardial infarction (RR 0.94, 95% CI 0.88 to 1.00), and stroke (RR 1.07, 95% CI 0.99 to 1.15). ACEIs were associated with an increased risk of angioedema (RR 2.79, 95% CI 1.05 to 7.42), whereas risk for hypotension and renal insufficiency was similar compared with active controls. Meta-regression analysis showed that the effect of ACEIs on outcomes remained consistent with age increasing >/=65 years. Sensitivity analysis excluding trials comparing ACEIs with angiotensin receptor blockers and heart failure trials yielded similar results, except for reduction in myocardial infarction. In conclusion, the efficacy of ACEIs was similar to active controls for mortality outcomes. Compared with placebo, there was evidence for reduction in cardiovascular outcomes; however, ACEIs failed to prevent stroke and increased the risk of angioedema, hypotension, and renal failure.

OBJECTIVES: Human immunodeficiency virus (HIV) seropositive individuals are predisposed to acute myocardial infarction (AMI). We sought to evaluate management strategies and outcomes of AMI in patients with HIV in the contemporary era. METHODS: We analyzed data from the National Inpatient Sample from 2002 to 2011 for patients admitted with AMI with or without HIV. Propensity-score matching was used to identify HIV seropositive AMI patients with similar characteristics who were managed invasively (cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft surgery [CABG]) or conservatively. The primary outcome was in-hospital all-cause mortality. RESULTS: Among 1,363,570 patients admitted with AMI, 3788 (0.28%) were HIV seropositive. The frequency of HIV diagnosis among AMI patients increased over time (0.20% in 2002 to 0.35% in 2011; P for trend <.001). Patients with HIV had lower odds of invasive management (adjusted odds ratio [OR], 0.59; 95% confidence interval [CI], 0.55-0.65) and were less likely to undergo CABG (OR, 0.66; 95% CI, 0.57-0.76) or receive drug-eluting stents (OR, 0.83; 95% CI, 0.76-0.92) than HIV-seronegative patients. Patients with HIV had higher in-hospital mortality (adjusted OR, 1.36; 95% CI, 1.13-1.64) than those without HIV. In a propensity-matched cohort of 1608 patients with HIV treated for AMI with invasive vs conservative management, invasive management was associated with lower in-hospital mortality (3.0% vs 8.2%; P<.001; OR, 0.34; 95% CI, 0.21-0.56). CONCLUSIONS: Disparities exist in management of AMI by HIV status. HIV seropositive patients were less likely to receive invasive management, CABG, and drug-eluting stents, and had higher in-hospital mortality vs patients without HIV.

An elevated resting heart rate has been unequivocally linked to adverse cardiovascular events. Conversely, a physiologically low heart rate may confer longevity benefits. Moreover, pharmacological heart rate lowering reduces cardiovascular outcomes in patients with heart failure, with the magnitude of the reduction associated with survival benefit. In contrast, pharmacological heart rate lowering paradoxically increases cardiovascular events in hypertension, possibly because it elicits a ventricular-vascular mismatch, leading to increased central systolic blood pressure (BP). By the same hemodynamic mechanism, pharmacological heart rate lowering also engenders an increase in central (aortic) BP in coronary heart disease and, as a consequence, fails to decrease myocardial oxygen consumption. Whether in heart failure, hypertension, or coronary heart disease, or even athletes, heart rate lowering consistently increases central systolic pressure. The increase in central systolic BP is prone to abolish the potential benefits of heart rate lowering interventions, possibly accounting for failure to reduce outcomes in patients with hypertension and coronary artery disease.