2008 April 21

Aliskiren.

Apr 212008

Aliskiren.

Drugs Today (Barc). 2007 Dec;43(12):849-55

Authors: Anderson DL

Aliskiren (CGP-60536 or SPP100) is the first oral direct renin inhibitor and the first new class of antihypertensive agents to be introduced in more than a decade. Aliskiren taken once a day, alone or in combination with other antihypertensive agents, has been shown to be effective in reducing blood pressure and is generally well tolerated. Based on an extensive clinical trials program, aliskiren was approved for the treatment of hypertension in March 2007 (as Tekturna; Novartis Pharmaceuticals, East Hanover, NJ, USA) by the U.S. Food and Drug Administration and in August 2007 (as Rasilez, Enviage, Sprimeo, Tekturna and Riprazo, all from Novartis) for the treatment of essential hypertension by the European Commission. Although the indication for aliskiren is treatment of essential hypertension, benefits similar to those demonstrated with certain angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are anticipated for aliskiren. Some of the 44 trials with aliskiren are listed in Table II. Inhibition of renin, which is the first and rate-limiting step in the renin-angiotensin pathway has theoretical advantages over either ACE inhibitors or ARBs.

PMID: 18174970 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

High-risk myocardial infarction in the young: the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial.

Am Heart J Start a Discussion »

Apr 212008

High-risk myocardial infarction in the young: the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial.

Am Heart J. 2008 Apr;155(4):706-11

Authors: Anderson RE, Pfeffer MA, Thune JJ, McMurray JJ, Califf RM, Velazquez E, White HD, Rouleau JL, Skali H, Maggioni A, Solomon SD

BACKGROUND: Advanced age is a well-established prognostic risk factor after acute myocardial infarction (AMI), yet approximately 10% of MIs occur in patients <45 years. We examined characteristics, cardiovascular outcomes, and the influence of risk factors on outcomes in young survivors of AMI. METHODS: Fourteen thousand seven hundred three patients enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial were divided into 3 age groups: 18 to < 45 (n = 803), 45 to < 65 (n = 6185), > or = 65 years (n = 7715). Multivariate Cox regression was used to compare cardiovascular event rates and assess the impact of risk factors on outcomes. RESULTS: The youngest patients had less diabetes, hypertension, and history of MI and were more likely to be male (18 to < 45 years, 88%; > or = 65 years, 59.1%), nonwhite (18 to < 45 years, 9.6%; > or = 65 years, 5%), current smokers (18 to < 45 years, 73.7%; > or = 65 years, 15.9%), obese (18 to < 45 years, 37.9%; > or = 65 years, 25.1%), and dyslipidemic at randomization (18 to < 45 years, 43.1%; > or = 65 years, 32.7%). Adjusted relative risks of smoking (18 to < 45 years, hazard ratio [HR] 1.6 [95% confidence interval {CI} 1.1-2.5]; > or = 45 years, HR 0.9 [95% CI 0.9-1.1]; P =.014) and hypertension (18 to < 45 years, HR 1.8 [95% CI 1.3-2.6]; > or = 45 years, HR 1.2 [95% CI 1.1-1.3]; P = .044) were higher in the young, with significant interactions observed between age and these risk factors. CONCLUSIONS: After AMI, risk factors and outcomes of the young differ substantively from their older counterparts. The influence of hypertension and smoking is more profound in the young, underscoring the need for aggressive risk factor modification post-AMI.

PMID: 18371480 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10).

Am Heart J Start a Discussion »

Apr 212008

Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10).

Am Heart J. 2008 Apr;155(4):712-7

Authors: Wilcox R, Kupfer S, Erdmann E,

BACKGROUND: Composite end points of major adverse cardiovascular events (MACEs) are standard measures for comparing treatment in large cardiovascular outcome studies. This analysis from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive) evaluated the effects of pioglitazone on the prespecified MACE end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE1) and on 6 post hoc MACE composites (various combinations of all-cause, cardiovascular, or cardiac mortality; plus nonfatal myocardial infarction; plus nonfatal stroke; and/or acute coronary syndrome) in patients with type 2 diabetes. METHODS: PROactive was a cardiovascular outcome study that randomized patients with type 2 diabetes to pioglitazone (n = 2605) or placebo (n = 2633), in addition to existing glucose-lowering and cardiovascular medications. Pioglitazone was titrated from 15 to 45 mg/d based upon tolerability. Mean follow-up was 34.5 months. RESULTS: At final visit, 257 (9.9%) pioglitazone-treated and 313 (11.9%) placebo-treated patients had a first event that contributed to the MACE1 end point (hazard ratio 0.82, 95% CI 0.70-0.97, P = .0201). There were statistically significant differences in favor of pioglitazone in 5 of the other MACE end points (P < .05) and a trend to benefit in the sixth (P = .052), with hazard ratios of 0.79 to 0.83. CONCLUSIONS: In patients with advanced type 2 diabetes at high risk for cardiovascular events, pioglitazone treatment resulted in significant risk reductions in MACE composite end points to 3 years.

PMID: 18371481 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Telmisartan, ramipril, or both in patients at high risk for vascular events.

N Engl J Med 1 Response »

Apr 212008

Telmisartan, ramipril, or both in patients at high risk for vascular events.

N Engl J Med. 2008 Apr 10;358(15):1547-59

Authors: , Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C

BACKGROUND: In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. METHODS: After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. RESULTS: Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). CONCLUSIONS: Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].).

PMID: 18378520 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Estimated glomerular filtration rate, inflammation, and cardiovascular events after an acute coronary syndrome.

Am Heart J Start a Discussion »

Apr 212008

Estimated glomerular filtration rate, inflammation, and cardiovascular events after an acute coronary syndrome.

Am Heart J. 2008 Apr;155(4):725-31

Authors: Mielniczuk LM, Pfeffer MA, Lewis EF, Blazing MA, de Lemos JA, Shui A, Mohanavelu S, Califf RM, Braunwald E

Both renal dysfunction and elevated levels of high-sensitivity C-reactive protein (CRP) are associated with a higher risk of cardiovascular (CV) outcomes. However, it remains to be established whether the prognostic value of impaired estimated glomerular filtration rate (GFR) remains after accounting for markers of inflammation. METHODS AND RESULTS: Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation in 4178 patients with non-ST or ST-elevation acute coronary syndromes, participating in the A to Z trial. The mean estimated GFR was 68 mL/min, with a median baseline CRP of 20.2 mg/L. Both an estimated GFR <60 mL/min (HR 2.13, 95% CI 1.7-2.6) and a CRP in the fourth quartile (HR 1.7, 95% CI 1.4-2.2) were strong univariate predictors of a CV event (composite of CV death, recurrent myocardial infarction, heart failure, or stroke). After adjusting for baseline CRP, GFR <60 mL/min remained a strong multivariate predictor for CV death (HR 1.82, 95% CI 1.1-2.97). Randomization to high-dose statin therapy was associated with a reduction in the CV composite (adjusted HR 0.69, 95% CI 0.5-0.95) irrespective of baseline renal function. CONCLUSIONS: In a population of patients without overt renal disease, moderate reductions in estimated GFR remain an important prognostic marker. This increased CV hazard associated with an estimated GFR <60 mL/min is independent and additive to markers of inflammation.

PMID: 18371483 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Quantitative troponin elevation does not provide incremental prognostic value beyond comprehensive risk stratification in patients with non-ST-segment elevation acute coronary syndromes.

Am Heart J Start a Discussion »

Apr 212008

Quantitative troponin elevation does not provide incremental prognostic value beyond comprehensive risk stratification in patients with non-ST-segment elevation acute coronary syndromes.

Am Heart J. 2008 Apr;155(4):718-24

Authors: Lim KD, Yan AT, Casanova A, Yan RT, Mendelsohn A, Jolly S, Fitchett DH, Langer A, Goodman SG,

BACKGROUND: The aim of this study was to evaluate whether quantitative cardiac troponin (cTn) assessment can improve risk stratification in a spectrum of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) using the validated Global Registry of Acute Cardiac Events (GRACE) risk model. METHODS: The Canadian ACS Registry II is a prospective, multicenter study that enrolled patients admitted to hospital with a suspected NSTE ACS within 24 hours of symptom onset. Of the total 2297 patients, those with elevated cTn (n = 1013) were further stratified into tertiles of cTn ranges. Our primary end point was death and our secondary end point was a composite of death or/and recurrent myocardial infarction at 1-year follow-up. RESULTS: Multivariable analysis adjusting for validated predictors of death confirmed the independent prognostic value of any abnormal cTn (vs normal) for death (adjusted odds ratio 2.28, 95% CI 1.49-3.49, P < .001) and for the composite outcome (adjusted odds ratio 2.18, 95% CI 1.61-2.95, P < .001) at 1 year. With quantitative assessment, the gradient of mortality risk with increasing cTn level was not evident after adjusting for other prognosticators. Quantitative (compared to qualitative) assessment of cTn level did not improve either the GRACE risk model discrimination for 1-year death. CONCLUSIONS: Any cTn elevation is associated with higher rate of death at 1 year, but its quantitative assessment did not prove as important as its mere presence as an independent long-term prognosticator in a nonclinical trial, "real-world" NSTE ACS population.

PMID: 18371482 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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