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Scott D Solomon

Publications and source records attributed to Scott D Solomon.

At least 55 records · Page 3Linked to original sources
PubMed2006

Increase in creatinine and cardiovascular risk in patients with systolic dysfunction after myocardial infarction.

Baseline renal function is a potent independent risk factor for adverse events after acute myocardial infarction (MI). Worsening renal function (WRF) has been shown to influence outcomes in the heart failure population, but its impact on cardiovascular risk in the post-MI period has not been well defined. For assessment of the prognostic importance of WRF, 2231 patients who had left ventricular dysfunction and were enrolled in the Survival and Ventricular Enlargement (SAVE) trial were studied. Patients were randomly assigned between 3 and 16 d (average 11 d) after acute MI to receive captopril or placebo; those with a serum creatinine of >2.5 mg/dl were excluded from SAVE. WRF was defined as an increase in creatinine of >0.3 mg/dl measured from baseline to 2 wk after randomization. The predictive value of WRF on cardiovascular morbidity and mortality was examined during 42 mo of follow-up. Paired serum creatinine measurements at baseline and 2 wk were available in 1854 patients. WRF occurred in 223 (12.0%) patients and was a stronger predictor of death (hazard ratio [HR] 1.46; 95% confidence interval [CI] 1.05 to 2.02) than baseline creatinine (HR 1.31; 95% CI 1.01 to 1.70). WRF also showed an increased risk for cardiovascular death (HR 1.62; 95% CI 1.14 to 2.30) and the composite end point (HR 1.32; 95% CI 1.03 to 1.70). When stratified by treatment, 104 (5.7%) and 116 (6.4%) patients with WRF in the placebo and captopril groups had no significant association between treatment group and WRF (P = 0.38). The risk for death associated with WRF was HR 1.63 (95% CI 1.05 to 2.52) in the placebo group compared with HR 1.33 (95% CI 0.81 to 2.21) in the captopril group (P = 0.49 for interaction). WRF as early as 2 wk after MI was not uncommon (12.0%) and was associated with increased mortality in patients without renal dysfunction at baseline. Patients who received captopril did not demonstrate more WRF than patients who received placebo. Monitoring serum creatinine in patients during the first few weeks after MI may help to identify those who are at highest risk and guide effective long-term therapeutic choices.

Cardiovascular Diseases↗
PubMed2006

Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.

BACKGROUND: Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function. METHODS AND RESULTS: We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13). CONCLUSIONS: Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.

Aged↗
PubMed2006

Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction.

AIMS: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). METHODS: The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. RESULTS: A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03-1.52; p=0.03) for prior AF and 1.32 (1.20-1.45; p<0.0001) for current AF. HR for major CV events was 1.15 (0.98-1.35; p=0.08) and 1.21 (1.12-1.31; p<0.0001). CONCLUSION: AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD.

Acute Disease↗
PubMed2006

Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program.

BACKGROUND: We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate <60 mL.min(-1).1.73 m(-2) compared with <30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and hospitalization, a relationship observed in patients with both reduced and preserved LVEF. There were 133 versus 69 deaths and 527 versus 352 hospitalizations per 1000 patient-years of follow-up in anemic versus nonanemic patients (both P<0.001). The effect of candesartan in reducing outcomes was independent of hemoglobin. CONCLUSIONS: Anemia was common in heart failure, regardless of LVEF. Lower hemoglobin was associated with higher LVEF yet was an independent predictor of adverse mortality and morbidity outcomes. In heart failure, the causes of anemia and the associations between anemia and outcomes are probably multiple and complex.

Aged↗
PubMed2006

Chronic recurrent myocardial ischemic injury is significantly attenuated by pre-emptive adeno-associated virus heme oxygenase-1 gene delivery.

OBJECTIVES: We assessed the hypothesis that overexpression of the antioxidant enzyme heme oxygenase (HO)-1 may protect against chronic recurrent ischemia/reperfusion injury. BACKGROUND: Multiple and recurring episodes of myocardial ischemia can result in significant myocardial damage, including myocyte death, fibrosis, and wall thinning, leading to impaired ventricular function and cardiac failure. METHODS: In this study we used a closed-chest rodent model of chronic recurring myocardial ischemia and reperfusion to investigate the efficacy of pre-emptive gene therapy in overexpressing the antioxidant enzyme HO-1, using adeno-associated virus (AAV)-2 as the delivery vector. RESULTS: We show that constitutive overexpression of HO-1 can prevent myocardial wall thinning, inflammation, fibrosis, and deterioration of cardiac function (as measured by echocardiography, histology, and immunohistochemistry) induced by repeated transient myocardial ischemia and reperfusion injury. With HO-1 therapy, there was a significant reduction in apoptosis as determined by levels of markers of survival proteins and terminal deoxynucleotidyltransferase dUTP nick end-labeling staining. This prevention of tissue damage was also associated with reduction in superoxide generation. CONCLUSIONS: Taken together we provide the first evidence of the therapeutic efficacy of pre-emptive AAV-HO-1 delivery for prevention against multiple ischemic injury. This approach protects myocytes by simultaneously activating protective response and inhibiting pathological left ventricular remodeling and, therefore, may be a useful cardio-protective strategy for patients with coronary artery disease at a high risk for recurrent myocardial ischemia.

Animals↗
PubMed2006

Left ventricular diastolic function following myocardial infarction.

An acute myocardial infarction causes a loss of contractile fibers which reduces systolic function. Parallel to the effect on systolic function, a myocardial infarction also impacts diastolic function, but this relationship is not as well understood. The two physiologic phases of diastole, active relaxation and passive filling, are both influenced by myocardial ischemia and infarction. Active relaxation is delayed following a myocardial infarction, whereas left ventricular stiffness changes depending on the extent of infarction and remodeling. Interstitial edema and fibrosis cause an increase in wall stiffness which is counteracted by dilation. The effect on diastolic function is correlated to an increased incidence of adverse outcomes. Moreover, patients with comorbid conditions that are associated with worse diastolic function tend to have more adverse outcomes after infarction. There are currently no treatments aimed specifically at treating diastolic dysfunction following a myocardial infarction, but several new drugs, including aldosterone antagonists, may offer promise.

Diastole↗
PubMed2006

Extent of coronary artery disease as a predictor of outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Left ventricular systolic dysfunction (LVSD) and heart failure (HF) are powerful predictors of poor outcome after acute myocardial infarction (MI). It is not known, however, whether the extent of coronary artery disease (CAD) independently influences cardiovascular (CV) outcomes in these high-risk patients. METHODS: In the VALIANT, 14703 patients were randomly assigned to receive either captopril monotherapy, valsartan monotherapy, or a valsartan and captopril combination between 0.5 and 10 days after acute MI complicated by LVSD, HF, or both. Cox proportional hazards models were used to evaluate the relation between the extent of CAD (the number of diseased vessels as assessed by angiography) and a range of CV outcomes and all-cause mortality. RESULTS: Coronary angiography data were available on 5742 (40%) of the 14703 randomized patients. Single-vessel disease was reported in 1955 patients (34%), 2-vessel disease in 1598 (28%), and 3-vessel disease in 2189 (38%). For all CV outcomes, the risk increased with the severity of CAD (P for trend < .002). A comparison of single-, 2-, and 3-vessel disease showed that, after adjusting for all known covariates, including revascularization and ejection fraction, 2-vessel disease was associated with a 40% increased hazard (P = .008) and 3-vessel disease was associated with an 85% increased hazard (P < .001) for all-cause mortality. The fully adjusted hazard ratios for death and other CV outcomes increased significantly with increasing extent of CAD. CONCLUSIONS: Increasing extent of CAD, as detected by angiography, is a significant and independent risk factor for adverse CV outcomes after MI complicated by HF, LVSD, or both. The observed risk was apparent even after excluding patients who had undergone revascularization.

Aged↗
PubMed2006

Rationale and design: the VALsartan In Diastolic Dysfunction (VALIDD) Trial: evolving the management of diastolic dysfunction in hypertension.

BACKGROUND: Although 50% of hypertensive patients in the community are estimated to have diastolic dysfunction, there is no specific guideline for diastolic dysfunction therapy at present despite the condition's clear association with increased cardiovascular risk. Although the efficacy of angiotensin II receptor blockers (ARBs) in hypertension and left ventricular hypertrophy regression has been established, the effect of angiotensin II receptor blockade on intrinsic parameters of diastolic function has not been evaluated in large-scale studies. METHODS: The VALIDD Trial is an investigator-initiated randomized, controlled, double-blind clinical trial on approximately 350 patients designed to explore whether antihypertensive therapy with the ARB valsartan, in addition to standard therapy, would improve intrinsic diastolic properties of the myocardium in patients with hypertension and evidence of diastolic dysfunction. The result of such therapy will be compared with placebo after 38 weeks of treatment. The primary efficacy variable is change in early diastolic lateral mitral annular relaxation velocity measured by tissue Doppler imaging on week 38. CONCLUSIONS: We expect the VALIDD Trial to provide novel insights into the specific effects of ARBs on diastolic dysfunction, as assessed by tissue Doppler imaging, in hypertensive patients. The trial may provide clinically useful data on whether such therapy can directly improve diastolic function in patients with hypertension.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Right ventricular dysfunction and adverse outcome in patients with advanced heart failure.

BACKGROUND: In patients with heart failure (HF) from left ventricular systolic dysfunction, the presence of coexistent right ventricular (RV) dysfunction is associated with poor exercise capacity and reduced survival. We sought to determine whether a simple measure of RV function, the RV myocardial performance index (RV MPI), is associated with adverse outcome in a population of advanced heart failure patients selected to receive cardiac resynchronization therapy (CRT). METHODS AND RESULTS: The RV MPI was measured on 77 consecutive preimplantation echocardiograms. The relationship between RV MPI and the end point of all-cause mortality, transplantation, or ventricular assist device placement was evaluated. The end point occurred in 28 patients (36%) during a median follow-up of 21 months. The median RV MPI was 0.73 (interquartile range 0.51-0.89). Worse RV function, as demonstrated by a higher RV MPI, was seen in those patients who reached the end point compared with those who did not (0.83 vs. 0.69, P = .004). The highest tercile of RV MPI was associated with a 3.3-fold increased risk of poor outcome (95% CI 1.3-8.5). Each 0.1 unit increase in RV MPI was associated with a 16% increased risk (95% CI 8-26). After adjusting for other echocardiographic variables, RV MPI remained significantly associated with the outcome. CONCLUSION: In a population of advanced HF patients selected to receive CRT, RV dysfunction, as assessed by the RV MPI, is associated with adverse outcome. Wider use of this simple nongeometric parameter may help to identify patients for whom options for further intervention should be carefully evaluated.

Aged↗
PubMed2006

Risk assessment in patients with depressed left ventricular function after myocardial infarction using the myocardial performance index--Survival and Ventricular Enlargement (SAVE) experience.

BACKGROUND: Myocardial performance index (MPI) is a noninvasive, quantitative Doppler measure of global cardiac function, integrating systolic and diastolic functions. The prognostic significance of MPI is less clear for cardiovascular (CV) events after myocardial infarction (MI) among individuals at high risk with depressed left ventricular (LV) systolic function. METHODS: We analyzed echocardiograms from 512 patients with depressed LV function after MI enrolled in the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy. Baseline MPI measures were obtainable in 226 patients. The cohort was separated by median MPI (0.50). MPI was related to baseline clinical and echocardiographic characteristics, ventricular remodeling, and subsequent CV events, including recurrent MI, heart failure, CV death, and a composite of all CV end points. RESULTS: An MPI of 0.5 or more was associated with larger infarct size and reduced LV systolic function at baseline; other baseline characteristics between the groups were similar. A total of 64 (28.3%) patients experienced CV events. Baseline MPI did not influence ventricular remodeling and did not modify the relationship between ventricular dilatation and CV events. After covariate adjustment, an MPI of 0.50 or higher remained an independent predictor for adverse CV events (hazard ratio [HR], 2.00, 95% confidence interval 1.17-3.43). CONCLUSIONS: An MPI of 0.50 or greater is an independent predictor for CV events after MI in patients with known LV dysfunction.

Cohort Studies↗
PubMed2006

Comparison of regional versus global assessment of left ventricular function in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction: the valsartan in acute myocardial infarction echocardiographic study.

BACKGROUND: Left ventricular (LV) ejection fraction (EF) and wall-motion index (WMI) have both been shown to be independent predictors of outcome after myocardial infarction (MI). OBJECTIVES: We sought to determine whether these two measurements of LV systolic function provide similar or complementary information about prognosis after MI. METHODS: Echocardiography was performed in 610 patients with LV dysfunction, heart failure, or both after MI enrolled in the Valsartan in Acute MI trial. LVEF was estimated by biplane Simpson's rule, and WMI was assessed using a 16-segment model in 502 patients with echocardiograms of sufficient quality for wall-motion assessment. RESULTS: Both LVEF and WMI were independent predictors of adverse outcome after MI. LVEF conferred no additional prognostic information in multivariable analysis including WMI (P = .39) or number of affected segments (P = .53), whereas WMI (P = .02) and total number of affected segments (P = .006) remained significant even when adjusting for LVEF. CONCLUSIONS: Assessment of regional dysfunction by WMI or the number of affected segments has slightly more prognostic value than LVEF in patients with LV dysfunction, heart failure, or both after MI. Regional assessment might be a more sensitive predictor of outcome than global assessment in patients with acute MI.

Aged↗
PubMed2006

Association of QRS duration and outcomes after myocardial infarction: the VALIANT trial.

BACKGROUND: Prolongation of the QRS duration has been shown to be associated with adverse outcomes among heart failure (HF) patients. The association of QRS duration with clinical outcomes in the post-myocardial infarction (MI) setting is less well defined. OBJECTIVES: To assess the prognostic significance of QRS duration prolongation on initial electrocardiogram after acute MI. METHODS: QRS duration was measured in 403 patients with MI complicated by left ventricular dysfunction, signs or symptoms of HF, or both, who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echo study. The cohort was divided into quartiles of QRS duration (<75 ms, 75-88 ms, 89-108 ms, >108 ms). The number of clinical events were determined and compared across the groups. RESULTS: Increasing QRS duration is associated with a higher incidence of HF, sudden death (SD), and cardiovascular (CV) death (P-trend <0.05) but not with stroke or recurrent MI. The univariate relative risks for HF, SD, and CV death with increasing QRS duration quartiles were 1.31 (95% CI, 1.06-1.64), 1.57 (95% CI, 1.03-2.40), and 1.31 (95% CI, 1.03-1.66), respectively, but QRS duration did not remain independently predictive of adverse outcome after adjusting for the 10 most predictive baseline covariates. Baseline end-diastolic and end-systolic volumes were larger and ejection fraction was lower in the higher QRS quartile groups. CONCLUSIONS: Prolonged QRS duration, even within the normal range, is associated with larger ventricular volumes, reduced systolic function, and an increased risk for development of HF, SD, and CV death after MI but appears to be a marker, rather than an independent predictor, for increased risk.

Aged↗
PubMed2006

Dietary sodium intake modulates myocardial relaxation responsiveness to angiotensin II.

Dietary sodium alters renovascular responsiveness to angiotensin II (Ang II) in normal subjects. Evidence supports a connection among dietary sodium, the rennin-angiotensin system, and myocardial function. The authors hypothesized that a similar relationship would exist in the heart, and that the pattern of responses would be qualitatively similar to the renal vasculature. Thirteen healthy volunteers (aged 38.6 +/- 4 years) entered a 2 week crossover design study (week 1, high sodium diet [HS] > 200 mmol Na/day; week 2, low sodium diet [LS], < 10 mmol Na/day) to investigate the influence of dietary sodium and Ang II on myocardial relaxation and renal blood flow (RBF). At the end of each study week, the authors assessed diastolic function (myocardial relaxation velocities [E'] using tissue Doppler imaging) and RBF (para-aminohippurate clearance) at baseline and after infusion of Ang II (3 ng/kg/min x 45 min). On HS diet, E' and RBF were higher than on LS diet (E' 14.0 +/- 1.2 vs 12.6 +/- 1.0 cm/s, P = 0.02; RBF 596 +/- 24 vs 563 +/- 26 mL/min, P = 0.02). Dietary sodium significantly modulated E' and RBF responsiveness to Ang II infusion in like manner. HS was associated with increased responsiveness compared with a blunted LS response (HS DeltaE' -1.4 +/- 0.4 cm/s vs LS DeltaE' -0.1 +/- 0.3 cm/s, P = 0.02; HS DeltaRBF -135.2 +/- 13.2 vs LS DeltaRBF -62.5 +/- 10.1 mL/min, P < 0.01). The authors describe for the first time that dietary sodium modulates myocardial relaxation and responsiveness to Ang II. It is important to consider dietary sodium intake when assessing diastolic function. Ang II may play a role in the interaction between dietary sodium and myocardial relaxation. Future research will investigate whether abnormalities in these mechanisms play a role in disorders of diastolic function.

Adult↗
PubMed2006

Characterization of microvascular dysfunction after acute myocardial infarction by cardiovascular magnetic resonance first-pass perfusion and late gadolinium enhancement imaging.

PURPOSE: While both first-pass perfusion and late gadolinium enhancement by cardiovascular magnetic resonance (CMR) can assess coronary microvascular status in acute myocardial infarction (AMI), there are only limited data on their respective diagnostic utility. We aim to evaluate: the utility of first-pass perfusion and late gadolinium enhancement imaging in the detection and quantification of microvascular dysfunction after reperfused acute myocardial infarction, using TIMI frame count (TIMI FC) as the reference standard of microvascular assessment; and their relationship with infarct size and ventricular function. METHODS: First-pass perfusion and late gadolinium enhancement imaging were performed in 25 consecutive AMI patients (84% men, age 58 +/- 10) within 72 h of successful reperfusion. We assessed the myocardial extent of microvascular dysfunction using the size of the perfusion defect on first-pass perfusion (PD%) and the hypoenhanced core region within late gadolinium enhancement (MDEcore%). PD%, MDEcore%, and TIMI FC were analyzed independently of each other and with blinding to clinical data. We adjusted PD% and MDEcore% to the myocardial mass subtended by the infarct-related artery according to the 16-segment model. RESULTS: Median infarct size involved 13.9% (interquartile range: 8.5 to 22.2%) of the left ventricle and median left ventricular ejection fraction was 52% (interquartile range: 43 to 61%). PD% demonstrated evidence of microvascular dysfunction more frequently (84% vs. 36% of patients, p < 0.002) and involved a larger myocardial extent (23.5 +/- 17.5% vs. 3.5 +/- 7.7%, p < 0.001) compared to MDEcore%. PD% had strong correlations with TIMI FC (Spearman rho = 0.62, p < 0.001) and infarct size (rho = 0.64, p < 0.001), and a moderate correlation with LVEF (rho = -0.39, p = 0.055). MDEcore% also correlated with TIMI FC (rho = 0.54, p = 0.005) and infarct size (rho = 0.52, p < 0.01) but not with LVEF (p = NS). CONCLUSIONS: PD% appeared to provide a stronger noninvasive assessment of the microvascular function than MDEcore% and correlated well with prognostic markers such as left ventricular ejection fraction and infarct size. Future studies should consider quantitative analyses of both first-pass perfusion and late gadolinium enhancement imaging in the evaluation of novel therapies targeted to the microvasculature of the infarct-related artery.

Aged↗
PubMed2006

Inhibiting the renin-angiotensin system in myocardial infarction and heart failure: lessons from SAVE, VALIANT and CHARM, and other clinical trials.

PURPOSE OF REVIEW: Inhibition of the renin-angiotensin-aldosterone system has become a cornerstone of modern heart failure and myocardial infarction therapy. This article will review the background and major clinical trials that have shaped this field over the past 15 years. RECENT FINDINGS: Major clinical trials have firmly established angiotensin converting enzyme (ACE) inhibitors as the standard of care in patients with heart failure and following myocardial infarction. Over the past several years, a number of trials have tested the hypothesis that an angiotensin II receptor blocker (ARB) could be as effective as, or more effective than, ACE inhibitors in these clinical settings. The results of these trials, while establishing a clear role for ARBs, have been subtly different in distinct patient populations. SUMMARY: The most recent trials of ARBs in heart failure and myocardial infarction patients suggest a role for angiotensin receptor blockers in patients with heart failure who are intolerant to ACE inhibitors and who are on optimal ACE inhibitor therapy. In patients with acute high-risk myocardial infarction, the VALIANT trial has established that the ARB was as effective as an ACE inhibitor following myocardial infarction. These studies have thus provided clinicians with alternatives to ACE inhibitors in these important clinical syndromes.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Cyclooxygenase-2 inhibitors and cardiovascular risk.

PURPOSE OF REVIEW: Cyclooxygenase-2 inhibitors, or coxibs, designed to provide comparable pain relief to traditional nonsteroidal anti-inflammatory drugs with reduced risk of gastrointestinal complications, have come under substantial recent scrutiny because of an increased likelihood of adverse cardiovascular events associated with their use. RECENT FINDINGS: Data concerning the cardiovascular risk associated with coxibs comes from three main sources: basic research demonstrating the potential for inhibitors of the cyclooxygenase-2 enzyme to promote a prothrombotic state; observational data suggesting an increased risk associated with the use of certain cyclooxygenase-2 inhibitors, and randomized trial data suggesting an increased risk associated with a variety of cyclooxygenase-2 inhibitors compared with either a traditional nonsteroidal anti-inflammatory drug, or placebo. SUMMARY: An increased risk of adverse cardiovascular events has been demonstrated with multiple cyclooxygenase-2 inhibitors, and this increased risk has led to the withdrawal from the market of all but one of these agents in the US. While several questions regarding the safety of coxibs remain, especially the role of dose in the increased risk and whether increased cardiovascular risk extends to traditional nonsteroidal anti-inflammatory drugs as well, clinicians should be cautioned about an increased possibility of adverse cardiovascular events in patients requiring therapy with coxibs.

Anti-Inflammatory Agents, Non-Steroidal↗