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Cardiac outcomes with submaximal normal stress echocardiography: a meta-analysis

Makani, Harikrishna; Bangalore, Sripal; Halpern, Dan; Makwana, Hetal G; Chaudhry, Farooq A
OBJECTIVES: The aim of the study was to evaluate the risk of cardiac events in patients with normal stress echocardiography (SE) who attained maximal age-predicted heart rate (APHR) compared with those who did not in the setting of both normal and abnormal SE. BACKGROUND: SE is an important tool in the risk stratification and prognosis of patients with known or suspected coronary artery disease (CAD). The prognostic value of a normal but submaximal SE (<85% of maximal APHR) is conflicting. METHODS: PubMed, EMBASE, and CENTRAL were searched from 1980 to September 2011 for SE studies reporting cardiac outcomes in patients with known or suspected CAD stratified by achieved APHR. Both hard events (cardiac death and myocardial infarction) and total cardiac events (revascularization procedures in addition to hard events) were analyzed separately. Data on all-cause mortality were obtained when available. RESULTS: Fourteen studies with 11,542 patients followed up for a mean duration of 32 months fulfilled the inclusion criteria. In 8 studies with 4,577 patients, the risk of hard events with normal SE (both exercise and dobutamine) was 70% higher in patients who achieved submaximal compared with those with maximal APHR (annualized event rate 2.08% vs. 0.77%; p = 0.0008; 95% confidence interval [CI]: 1.25 to 2.31). In 7 studies with 5,798 patients, the risk of total cardiac events with normal SE (both exercise and dobutamine) was 127% higher in patients who achieved submaximal compared with those with maximal APHR (annualized event rate 1.87% vs. 1.02%; p < 0.0001; 95% CI: 1.54 to 3.34). The risk of total cardiac events was 278% higher in patients with abnormal SE with submaximal APHR compared with those with normal SE with submaximal APHR (p < 0.0001; 95% CI: 2.81 to 5.08). There was a trend toward increased all-cause mortality in patients with normal SE with submaximal compared with maximal APHR (relative risk: 1.36; p = 0.15; 95% CI: 0.89 to 2.09). CONCLUSIONS: Patients with submaximal APHR in the setting of normal SE have a higher risk of cardiovascular events than those who attained maximal stress test. Thus, the results of submaximal APHR in the setting of normal SE should be taken into consideration for more accurate risk stratification and prognosis.
PMID: 22981557
ISSN: 0735-1097
CID: 180130

beta-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease

Bangalore, Sripal; Steg, Gabriel; Deedwania, Prakash; Crowley, Kevin; Eagle, Kim A; Goto, Shinya; Ohman, E Magnus; Cannon, Christopher P; Smith, Sidney C; Zeymer, Uwe; Hoffman, Elaine B; Messerli, Franz H; Bhatt, Deepak L
CONTEXT: beta-Blockers remain the standard of care after a myocardial infarction (MI). However, the benefit of beta-blocker use in patients with coronary artery disease (CAD) but no history of MI, those with a remote history of MI, and those with only risk factors for CAD is unclear. OBJECTIVE: To assess the association of beta-blocker use with cardiovascular events in stable patients with a prior history of MI, in those with CAD but no history of MI, and in those with only risk factors for CAD. DESIGN, SETTING, AND PATIENTS: Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14,043), known CAD without MI (n = 12,012), or those with CAD risk factors only (n = 18,653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009. MAIN OUTCOME MEASURES: The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. RESULTS: Among the 44,708 patients, 21,860 were included in the propensity score-matched analysis. With a median follow-up of 44 months (interquartile range, 35-45 months), event rates were not significantly different in patients with beta-blocker use compared with those without beta-blocker use for any of the outcomes tested, even in the prior MI cohort (489 [16.93%] vs 532 [18.60%], respectively; hazard ratio [HR], 0.90 [95% CI, 0.79-1.03]; P = .14). In the CAD without MI cohort, the associated event rates were not significantly different in those with beta-blocker use for the primary outcome (391 [12.94%]) vs without beta-blocker use (405 [13.55%]) (HR, 0.92 [95% CI, 0.79-1.08]; P = .31), with higher rates for the secondary outcome (1101 [30.59%] vs 1002 [27.84%]; odds ratio [OR], 1.14 [95% CI, 1.03-1.27]; P = .01) and for the tertiary outcome of hospitalization (870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30]; P = .01). In the cohort with CAD risk factors only, the event rates were higher for the primary outcome with beta-blocker use (467 [14.22%]) vs without beta-blocker use (403 [12.11%]) (HR, 1.18 [95% CI, 1.02-1.36]; P = .02), for the secondary outcome (870 [22.01%] vs 797 [20.17%]; OR, 1.12 [95% CI, 1.00-1.24]; P = .04) but not for the tertiary outcomes of MI (89 [2.82%] vs 68 [2.00%]; HR, 1.36 [95% CI, 0.97-1.90]; P = .08) and stroke (210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P = .06). However, in those with recent MI (</=1 year), beta-blocker use was associated with a lower incidence of the secondary outcome (OR, 0.77 [95% CI, 0.64-0.92]). CONCLUSION: In this observational study of patients with either CAD risk factors only, known prior MI, or known CAD without MI, the use of beta-blockers was not associated with a lower risk of composite cardiovascular events.
PMID: 23032550
ISSN: 0098-7484
CID: 179103

Age and Gender Differences in Quality of Care and Outcomes for Patients with ST-segment Elevation Myocardial Infarction

Bangalore, Sripal; Fonarow, Gregg C; Peterson, Eric D; Hellkamp, Anne S; Hernandez, Adrian F; Laskey, Warren; Peacock, W Frank; Cannon, Christopher P; Schwamm, Lee H; Bhatt, Deepak L
BACKGROUND: Young patients (aged
PMID: 22748404
ISSN: 0002-9343
CID: 178833

Outcomes with various drug eluting or bare metal stents in patients with diabetes mellitus: mixed treatment comparison analysis of 22 844 patient years of follow-up from randomised trials

Bangalore, Sripal; Kumar, Sunil; Fusaro, Mario; Amoroso, Nicholas; Kirtane, Ajay J; Byrne, Robert A; Williams, David O; Slater, James; Cutlip, Donald E; Feit, Frederick
OBJECTIVES: To evaluate the efficacy and safety of currently used drug eluting stents compared with each other and compared with bare metal stents in patients with diabetes. DESIGN: Mixed treatment comparison meta-analysis. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and CENTRAL were searched for randomised clinical trials, until April 2012, of four durable polymer drug eluting stents (sirolimus eluting stents, paclitaxel eluting stents, everolimus eluting stents, and zotarolimus eluting stents) compared with each other or with bare metal stents for the treatment of de novo coronary lesions and enrolling at least 50 patients with diabetes. PRIMARY OUTCOMES: Efficacy (target vessel revascularisation) and safety (death, myocardial infarction, stent thrombosis). RESULTS: From 42 trials with 22 844 patient years of follow-up, when compared with bare metal stents (reference rate ratio 1) all of the currently used drug eluting stents were associated with a significant reduction in target vessel revascularisation (37% to 69%), though the efficacy varied with the type of stent (everolimus eluting stents approximately sirolimus eluting stents>paclitaxel eluting stents approximately zotarolimus eluting stent>bare metal stents). There was about an 87% probability that everolimus eluting stents were the most efficacious compared with all others, though there were limited usable data for the zotarolimus eluting Resolute stent in patients with diabetes. Moreover, there was no increased risk of any safety outcome (including very late stent thrombosis) with any drug eluting stents compared with bare metal stents. There was about a 62% probability that the everolimus eluting stent was the safest stent for the outcome of "any" stent thrombosis. CONCLUSIONS: Among patients with diabetes treated with coronary stents all currently available drug eluting stents were efficacious without compromising safety compared with bare metal stents. There were relative differences among the drug eluting stents, such that the everolimus eluting stent was the most efficacious and safe.
PMCID:3415955
PMID: 22885395
ISSN: 0959-8146
CID: 174407

Meta-analysis of randomized trials of angioedema as an adverse event of Renin-Angiotensin system inhibitors

Makani, Harikrishna; Messerli, Franz H; Romero, Jorge; Wever-Pinzon, Omar; Korniyenko, Aleksander; Berrios, Ronaldo Sevilla; Bangalore, Sripal
Angioedema is a rare, potentially life-threatening adverse event of renin-angiotensin system inhibitors. The objective of the present study was to determine the risk of angioedema from randomized clinical trials. A PubMed/CENTRAL/EMBASE search was made for randomized clinical trials from 1980 to October 2011 in patients on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or direct renin inhibitor (DRI). Trials with a total number of patients >/=100 and a duration of >/=8 weeks were included for analysis. Incidence of angioedema was pooled by weighing the incident rate of each trial by the inverse of the variance. Twenty-six trials with 74,857 patients in the ACE inhibitor arm with 232,523 person-years of follow-up, 19 trials with 35,479 patients on ARB with 122,293 person-years of follow-up, and 2 trials with 5,141 patients on DRI with 1,735 person-years of follow-up met the inclusion criteria and were included in the analysis. In head-to-head comparison in 7 trials, risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs (95% confidence interval [CI] 1.5 to 3.3). With ACE inhibitors and ARBs, incidence of angioedema was higher in heart failure trials compared to hypertension or coronary artery disease trials without heart failure (p <0.0001). Weighted incidence of angioedema with ACE inhibitors was 0.30% (95% CI 0.28 to 0.32) compared to 0.11% (95% CI 0.09 to 0.13) with ARBs, 0.13% (95% CI 0.08 to 0.19) with DRIs, and 0.07% with placebo (95% CI 0.05 to 0.09). In conclusion, incidence of angioedema with ARBs and DRI was <1/2 than that with ACE inhibitors and not significantly different from placebo. Incidence of angioedema was higher in patients with heart failure compared to those without heart failure with ACE inhibitors and ARBs.
PMID: 22521308
ISSN: 0002-9149
CID: 174532

Percutaneous coronary intervention versus optimal medical therapy in stable coronary artery disease: a systematic review and meta-analysis of randomized clinical trials

Pursnani, Seema; Korley, Frederick; Gopaul, Ravindra; Kanade, Pushkar; Chandra, Newry; Shaw, Richard E; Bangalore, Sripal
BACKGROUND: The role of percutaneous coronary intervention (PCI) in the management of stable coronary artery disease remains controversial. Given advancements in medical therapies and stent technology over the last decade, we sought to evaluate whether PCI, when added to medical therapy, improves outcomes when compared with medical therapy alone. METHODS AND RESULTS: We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and CENTRAL databases, until January 2012, for randomized clinical trials comparing revascularization with PCI to optimal medical therapy (OMT) in patients with stable coronary artery disease. The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular death, nonfatal myocardial infarction, subsequent revascularization, and freedom from angina. Primary analyses were based on longest available follow-up with secondary analyses stratified by trial duration, with short-term (/=5 years) time points. We identified 12 randomized clinical trials enrolling 7182 participants who fulfilled our inclusion criteria. For the primary analyses, when compared with OMT, PCI was associated with no significant improvement in mortality (risk ratio [RR], 0.85; 95% CI, 0.71-1.01), cardiac death (RR, 0.71; 95% CI, 0.47-1.06), nonfatal myocardial infarction (RR, 0.93; 95% CI, 0.70-1.24), or repeat revascularization (RR, 0.93; 95% CI, 0.76-1.14), with consistent results over all follow-up time points. Sensitivity analysis restricted to studies in which there was >50% stent use showed attenuation in the effect size for all-cause mortality (RR, 0.93; 95% CI, 0.78-1.11) with PCI. However, for freedom from angina, there was a significant improved outcome with PCI, as compared with the OMT group (RR, 1.20; 95% CI, 1.06-1.37), evident at all of the follow-up time points. CONCLUSIONS: In this most rigorous and comprehensive analysis in patients with stable coronary artery disease, PCI, as compared with OMT, did not reduce the risk of mortality, cardiovascular death, nonfatal myocardial infarction, or revascularization. PCI, however, provided a greater angina relief compared with OMT alone, larger studies with sufficient power are required to prove this conclusively.
PMID: 22872053
ISSN: 1941-7640
CID: 183542

Vascular closure device failure in contemporary practice

Vidi, Venkatesan D; Matheny, Michael E; Govindarajulu, Usha S; Normand, Sharon-Lise T; Robbins, Susan L; Agarwal, Vikram V; Bangalore, Sripal; Resnic, Frederic S
OBJECTIVES: The goal of this study was to assess the frequency and predictors of vascular closure device (VCD) deployment failure, and its association with vascular complications of 3 commonly used VCDs. BACKGROUND: VCDs are commonly used following percutaneous coronary intervention on the basis of studies demonstrating reduced time to ambulation, increased patient comfort, and possible reduction in vascular complications as compared with manual compression. However, limited data are available on the frequency and predictors of VCD failure, and the association of deployment failure with vascular complications. METHODS: From a de-identified dataset provided by Massachusetts Department of Health, 23,813 consecutive interventional coronary procedures that used either a collagen plug-based (n = 18,533), a nitinol clip-based (n = 2,284), or a suture-based (n = 2,996) VCD between June 2005 and December 2007 were identified. The authors defined VCD failure as unsuccessful deployment or failure to achieve immediate access site hemostasis. RESULTS: Among 23,813 procedures, the VCD failed in 781 (3.3%) procedures (2.1% of collagen plug-based, 6.1% of suture-based, 9.5% of nitinol clip-based VCDs). Patients with VCD failure had an excess risk of "any" (7.7% vs. 2.8%; p < 0.001), major (3.3% vs. 0.8%; p < 0.001), or minor (5.8% vs. 2.1%; p < 0.001) vascular complications compared with successful VCD deployment. In a propensity score-adjusted analysis, when compared with collagen plug-based VCD (reference odds ratio [OR] = 1.0), nitinol clip-based VCD had 2-fold increased risk (OR: 2.0, 95% confidence interval [CI]: 1.8 to 2.3, p < 0.001) and suture-based VCD had 1.25-fold increased risk (OR: 1.25, 95% CI: 1.2 to 1.3, p < 0.001) for VCD failure. VCD failure was a significant predictor of subsequent vascular complications for both collagen plug-based VCD and nitinol clip-based VCD, but not for suture-based VCD. CONCLUSIONS: VCD failure rates vary depending upon the type of VCD used and are associated with significantly higher vascular complications as compared with deployment successes.
PMCID:3427601
PMID: 22917455
ISSN: 1876-7605
CID: 177227

Visit-to-visit variability in low density lipoprotein-cholesterol and risk of cardiovascular outcomes: insights from the treating to new targets trial [Meeting Abstract]

Bangalore, S.; Breazna, A.; Demicco, D.; Messerli, F. H.
ISI:000308012407056
ISSN: 0195-668x
CID: 179165

Do angiotensin receptor blockers prevent myocardial infarctions as well as other initial therapies?

Singh, Amita; Bangalore, Sripal
PURPOSE OF REVIEW: As their introduction, angiotensin receptor blockers (ARBs) have been widely promulgated as an acceptable alternative to angiotensin-converting enzyme inhibitors (ACEIs). Beyond a simple antihypertensive effect, ACEIs have been shown to reduce the rates of myocardial infarction (MI), stroke, and new-onset heart failure, and appear to have a 'blood pressure independent' effect. Given the shared mechanism of preventing action of angiotensin II, the effects of ARB therapy on reduction in cardiovascular and renal outcomes were anticipated to be equal to that of ACEI. RECENT FINDINGS: The role of ARBs in the prevention of MI has not only been disputed, but also has at times cast the class as a causative agent in increasing the risk of MI. This potentially deleterious effect was proposed after results from the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, in which the use of valsartan (ARB) was compared with amlodipine in patients at high cardiovascular disease risk, found an excess of MIs among patients in the valsartan arm. Subsequent clinical trials and meta-analyses have largely laid to rest the question of whether ARBs contribute to cardiovascular risk. SUMMARY: The definitive answer of whether ARBs are effective, if at all, in preventing MI remains difficult to parse out. Current evidence from newer clinical trials and comprehensive meta-analyses suggests that ARBs, while effective antihypertensive agents that protect against risk of stroke, renal disease, diabetes, and heart failure, are likely to have a neutral effect upon reduction of MI when compared with other antihypertensive agents.
PMID: 22525329
ISSN: 0268-4705
CID: 169505

Which, if any, antihypertensive agents cause cancer?

Singh, Amita; Bangalore, Sripal
PURPOSE OF REVIEW: Preclinical studies have elucidated molecular pathways by which specific classes of antihypertensive agents may promote, or protect, against tumor development and progression. Observational studies have proposed an association between antihypertensive agents and cancer, but due to limitations inherent to their study design cannot alone establish causality. Moreover, prospective randomized clinical trials (RCT) of antihypertensive agents have focused on cardiovascular and renal outcomes, rather than incidence of new cancer, making inference from RCTs problematic. The purpose of this review was to highlight the classes of medications implicated in increased cancer risk, with a focus on angiotensin receptor blocker (ARB) therapy, as recent published data surrounding their use remains the most controversial. RECENT FINDINGS: A recent meta-analysis of RCTs found a significant increase in the risk of cancer with ARBs when compared with control, eliciting a safety review by the Food and Drug Administration. Subsequently, more robust meta-analyses have refuted these findings, demonstrating no association between any of the currently used antihypertensive agents and cancer. Despite the complex methodology of these meta-analyses, the randomized trials used for analysis are fraught with inconsistencies, including the availability of cancer outcomes, a brief time to follow-up as compared with the latency of cancer, and heterogeneous use of antihypertensive agents. SUMMARY: The medical literature has long hypothesized potentially carcinogenic effects of antihypertensive agents, but to date there is no convincing evidence that any of the individual antihypertensives in clinical use, at the dosages and duration tested, lead to higher rates of cancer.
PMID: 22565138
ISSN: 0268-4705
CID: 169509