Multivessel Revascularization Does Not Increase Contrast-Induced Acute Kidney Injury Incidence in Acute Myocardial Infarction: A Meta-Analysis.

BACKGROUND: Recent studies and meta-analysis have shown that complete revascularization (CR) compared with infarct-related artery revascularization (IRA) during percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) is associated with decreased mortality. However, it is unclear if CR versus IRA in STEMI during indexed hospitalization is associated with risk of contrast-induced acute kidney injury (CI-AKI). METHODS: A database search was conducted for all randomized controlled trials that enrolled STEMI patients and compared CR versus IRA and reported CI-AKI. Comprehensive Meta-Analysis Version 2.0 (Wiley, Chichester) was used to determine summary effect size with a fixed-effect model and expressed as a risk ratio with 95 % confidence intervals. RESULTS: A total of four trials were identified and had a mean follow-up of 24.5 ± 9.9 months, a total sample size of 1537, a mean age of 63.8 ± 1.2 versus 64.2 ± 2.1 years, 31.2 ± 5.3 versus 30.1 ± 4.7 % three-vessel disease, and 33.7 ± 4.1 versus 37.2 ± 4.5 % anterior STEMI in the CR versus IRA groups, respectively. A total of 276.7 ± 25.2 versus 186.7 ± 15.3 mL contrast was used in the CR versus IRA respectively (p = 0.006). There were no statistical significant differences between the two groups in the reported incidence of CI-AKI (1.3 % CR vs. 1.9 % IRA; p = 0.4), major bleeding (1.7 % CR vs. 2.5 % IRA; p = 0.4) and stroke (1.1 % CR vs. 0.4 % IRA; p = 0.24). However, there was a significantly increased incidence of cardiovascular death (2.0 % CR vs. 4.7 % IRA; p = 0.01) and ischemia-driven revascularization (6.2 % CR vs. 18.3 % IRA; p < 0.01). CONCLUSION: In the index hospitalization, CR in STEMI patients is associated with significant risk reduction in cardiac death and revascularization and a non-significant reduced trend of CI-AKI, despite increased use of contrast when compared with IRA.

Safety and efficacy of everolimus-eluting bioresorbable vascular scaffolds versus durable polymer everolimus-eluting metallic stents assessed at 1-year follow-up: A systematic review and meta-analysis of studies.

BACKGROUND: The Absorb bioresorbable vascular scaffold (BVS) was developed to address long-term safety issues of metallic drug-eluting stents. However, it may be associated with an increased event risk during the first year. METHODS: A systematic literature search was performed (in MEDLINE/PubMed, Cochrane CENTRAL, EMBASE, and scientific meeting abstracts) to identify studies that compared BVS and cobalt-chromium durable polymer everolimus-eluting stents (EES). For randomized clinical trials and non-randomized propensity score matched studies that reported 1-year outcome data, fixed/random-effects models were used to generate pooled estimates of outcomes, presented as odds ratios (OR) with 95%-confidence intervals (CI). RESULTS: The 1-year follow-up data of 6 trials with 5588 patients were analyzed. A device-oriented composite endpoint (DOCE - cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR)) was reached by 308 BVS or EES patients (195/3253 vs. 113/2315). Meta-analysis showed that patients who received BVS had an increased risk of MI (4.3% vs. 2.3%; OR:1.63, 95%-CI: 1.18-2.25, p<0.01) and definite-or-probable scaffold thrombosis (1.3% vs. 0.6%; OR:2.10, 95%-CI: 1.13-3.87, p=0.02). However, there was no significant between-group difference in risk of DOCE (6.0% vs. 4.9%; OR:1.19, 95%-CI: 0.94-1.52, p=0.16), cardiac death (0.8% vs. 0.7%; OR:1.14, 95%-CI: 0.54-2.39, p=0.73), or TLR (2.5% vs. 2.5%; OR: 0.98, 95%-CI:0.69-1.40, p=0.92). CONCLUSIONS: During the first year of follow-up, patients treated with BVS had a higher incidence of MI and scaffold thrombosis. The risk of DOCE was not significantly different. As BVS may pay off later, future robust data on long-term clinical outcome will be of paramount importance.

Polypharmacy in Older Adults With Hypertension: A Comprehensive Review.

Older adults are more likely to take more than two medications for medical conditions, and polypharmacy is associated with increased risk of adverse events (fall injury, hyperkalemia and hypokalemia, heart failure, and blood pressure exacerbation), polypharmacy mismanagement, drug-drug interaction, and increased costs. Knowledge of drugs that interact with known antihypertensive agents is paramount to avoiding or reducing adverse events, hospitalizations, and health care dollars. Innovative approaches such as use of a fixed-dose combination pill, ingestible sensor system, electronic reminder system, medical audits, and the integration of a pharmacist in the care of patients should be implemented to avoid polypharmacy mismanagement.

Long-Term Anti-Hypertensive Therapy and Stroke Prevention: A Meta-Analysis.

BACKGROUND: Stroke causes approximately 6.7 million deaths worldwide per year and is the second leading cause of death. Pharmacotherapy for hypertension, an independent risk factor for stroke, significantly reduces the incidence of stroke. Although prior meta-analyses demonstrate various antihypertensive classes are superior to placebo in reducing stroke risk, which class is most effective is unclear. METHODS: We conducted a systematic MEDLINE search including only randomized controlled trials (RCT) of antihypertensive medications published between 1999 and 2014 in adults with stroke as a primary or secondary outcome. Five classes compared against all others were angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), ß-adrenoceptor antagonists (ß-blockers), calcium channel blockers (CCBs), and thiazide or thiazide-like diuretics (T-TLDs). Among 17 RCTs with 31 comparative arms, risk ratio was used to assess effect size, and a fixed- and random-effect model was used to calculate summary effect size, utilizing comprehensive meta-analysis statistical software version 2.0. RESULTS: The 251,853 subjects (46 ± 11.4 % female; mean age 67.2 ± 6.8 years), were grouped as follows: ACEI 52,887; ARB 7278; ACEI/ARB 60,165; ß-blocker 24,099; CCB 98,950; and T-TLD 68,639. The mean follow-up was 42.9 ± 15 months. A random-effect model was used to assess for summary effect size in ACEI, ACEI/ARB, ARB, and T-TLD groups. The summary risk ratio for stroke occurrence in the different antihypertensive drug classes were as follows: ACEIs 1.01 (95 % confidence interval [CI] 0.81-1.27; p = 0.92); ACEIs/ARBs 0.94 (95 % CI 0.78-1.13; p = 0.51); T-TLDs 0.90 (95 % CI 0.75-1.08; p = 0.25); ARBs 0.83 (95 % CI 0.59-1.18; p = 0.30); ß-blockers 1.42 (95 % CI 1.26-1.61; p < 0.01); and CCBs 0.83 (95 % CI 0.79-0.89; p < 0.01). CONCLUSION: Among the antihypertensive classes, CCBs were most effective in reducing the long-term incidence of stroke, whereas ß-blockers were associated with significantly increased risk.

Effects of low-dose thiazide diuretics on fasting plasma glucose and serum potassium-a meta-analysis.

This study is a meta-analysis of the metabolic profile (fasting plasma glucose and serum potassium) of low-dose thiazide and thiazide-like diuretics. The meta-analysis involved 10 randomized controlled clinical trials with a total sample size of 17,636 and 17,947 for the potassium and glucose arms respectively. The random effect model was used to calculate the odds ratio with 95 percent confidence interval. The cumulative mean change of fasting plasma glucose was +0.20 mmol/L (+3.6 mg/dL) for the diuretic arm versus +0.12 mmol/L (+2.2 mg/dL) for the comparator arm. The cumulative mean change of serum potassium was -0.22 mmol/L (-0.22 mEq/L) for the diuretic arm versus +0.05 mmol/L (+0.05 mEq/L) for the comparator arm. The aggregate odds ratio for having higher fasting plasma glucose in subjects on low-dose thiazide versus non-thiazide antihypertensive was 1.22 (1.11 to 1.33; P < .01). The odds ratio for having a lower serum potassium in subjects on low-dose thiazide versus non-thiazide antihypertensive was 0.36 (0.27 to 0.49; P < .01). The magnitude of the observed change in fasting plasma glucose associated with low-dose thiazide diuretic use, while statistically significant, does not appear to place patients at clinically significant risk. On the other hand, the observed change in serum potassium was also statistically significant, and may be clinically significant in patients whose baseline potassium concentration is low or low-normal, and could predispose at-risk patients, such as those with ischemic heart disease, to ventricular arrhythmias.

Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling.

BACKGROUND: MicroRNAs (miRNAs) play a key role in the development of heart failure, and recent studies have shown that the muscle-specific miR-1 is a key regulator of cardiac hypertrophy. We tested the hypothesis that chronic restoration of miR-1 gene expression in vivo will regress hypertrophy and protect against adverse cardiac remodeling induced by pressure overload. METHODS AND RESULTS: Cardiac hypertrophy was induced by left ventricular pressure overload in male Sprague-Dawley rats subjected to ascending aortic stenosis. When the hypertrophy was established at 2 weeks after surgery, the animals were randomized to receive either an adeno-associated virus expressing miR-1 (AAV9.miR-1) or green fluorescent protein (GFP) as control (AAV9.GFP) via a single-bolus tail-vein injection. Administration of miR-1 regressed cardiac hypertrophy (left ventricular posterior wall thickness,; 2.32±0.08 versus 2.75±0.07 mm, P<0.001) and (left ventricular septum wall thickness, 2.23±0.06 versus 2.54±0.10 mm, P<0.05) and halted the disease progression compared with control-treated animals, as assessed by echocardiography (fractional shortening, 37.60±5.01% versus 70.68±2.93%, P<0.05) and hemodynamic analyses (end-systolic pressure volume relationship/effective arterial elastance, 1.87±0.46 versus 0.96±0.38, P<0.05) after 7 weeks of treatment. Additionally, miR-1 replacement therapy lead to a marked reduction of myocardial fibrosis, an improvement in calcium handling, inhibition of apoptosis, and inactivation of the mitogen-activated protein kinase signaling pathways, suggesting a favorable effect on preventing the maladaptive ventricular remodeling. We also identified and validated a novel bona fide target of miR-1, Fibullin-2 (Fbln2), a secreted protein implicated in extracellular matrix remodeling. CONCLUSIONS: Taken together, our findings suggest that restoration of miR-1 gene expression is a potential novel therapeutic strategy to reverse pressure-induced cardiac hypertrophy and prevent maladaptive cardiac remodeling.