IDEAL Study

Clinical Question:
Does intensive lowering of LDL-C reduce the risks of cardiovascular disease among patients with previous myocardial infarction?

Bottom Line:
In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions.

Reference:
High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial.Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, Larsen ML, Bendiksen FS, Lindahl C, Szarek M, Tsai J; Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group.JAMA. 2005 Nov 16;294(19):2437-45.

Study Design:
Randomized Controlled Trial (prospective, open-label)

Synopsis:
Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n = 4439), or usual-dose simvastatin (20 mg/d; n = 4449). Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI, 0.78-1.01; P = .07). Nonfatal acute MI occurred in 321 (7.2%) and 267 (6.0%) in the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% CI, 0.77-0.98; P = .02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.76-0.91; P<.001). Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% CI, 0.73-1.15; P = .47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% CI, 0.85-1.13; P = .81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (P<.001). Serious myopathy and rhabdomyolysis were rare in both groups.

LDL Cholesterol "The lower the better" in patient with acute and chronic cardiovascular disease

Clinical Question:
Are there evidence that statin is effective in reducing death on patient with acute and chronic cardiovascular disease?

Bottom Line:
For patients at high risk of coronary artery disease there is growing evidence for the concept of 'the lower, the better' regarding LDL cholesterol levels. The target values for LDL cholesterol of less than 1.8 mmol/l (<70 mg/dl) should be considered for all patients with coronary artery disease or equivalent coronary risk.Ongoing trials are further investigating the safety of lower target values in patients at various risk of coronary artery disease.

Reference:
Statin therapy for prevention and treatment of acute and chronic cardiovascular disease: update on recent trials and metaanalyses.Briel M, Nordmann AJ, Bucher HC. Curr Opin Lipidol. 2005 Dec;16(6):601-5.

Study Design:
Metaanalysis (Randomized Controlled Trials)

Synopsis:
The author summarized evidence from recent clinical trials and metaanalyses on the efficacy of statin therapy to reduce death, myocardial infarction and stroke, and to review the effects of statins in patients with low LDL cholesterol, diabetes, end-stage renal disease, and acute coronary syndrome. In large metaanalyses of randomized controlled trials relative risk reductions from statins compared with placebo for patients with manifest or with risk factors for coronary artery disease were 13% for overall mortality, 26% for fatal and nonfatal myocardial infarction, and 18% for fatal and nonfatal stroke. Evidence from large trials suggests that patients with type II diabetes compared with patients without diabetes have similar risk reductions from statins for cardiovascular events, but this benefit is not seen in patients with diabetes and end-stage renal disease. In patients with acute coronary syndrome, early treatment with high-dose atorvastatin reduces cardiovascular morbidity after the first 4 months following the event, but the impact on mortality endpoints remains less clear. Results from recent trials in patients with stable coronary artery disease or type II diabetes suggest that statins provide benefit at considerable low LDL cholesterol levels. Therefore, target values for LDL cholesterol of less than 1.8 mmol/l (<70 mg/dl) should be considered for all patients with coronary artery disease or equivalent coronary risk.

The Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) Study

Bottom Line:
The combination of amlodipine besylate/benazepril HCl given to patients with stage 2 systolic hypertension resulted in significantly greater reductions in blood pressure and pulse pressure than those seen with monotherapy and was at least as well tolerated as the separate components. This data supports the recommendation of the JNC 7 for the use of combination therapy in patients with stage 2 hypertension.

Reference:
Efficacy of Combination Therapy for Systolic Blood Pressure in Patients With Severe Systolic Hypertension: The Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) Study.Neutel JM, Smith DH, Weber MA, Schofield L, Purkayastha D, Gatlin M.J Clin Hypertens (Greenwich). 2005 Nov;7(11):641-6

Synopsis:
Systolic hypertension is predominant among patients over 50 years of age, is a more important cardiovascular risk factor than diastolic blood pressure, and is more difficult to control than diastolic blood pressure. Consequently, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends combination therapy as first-line treatment for patients with stage 2 hypertension. In the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study, 24-hour ambulatory blood pressure monitoring was used to identify patients with systolic hypertension and to determine the impact of 8 weeks of treatment with either amlodipine besylate/benazepril HCl 5/20 mg combination therapy (n=149), amlodipine besylate 5 mg (n=146), or benazepril HCl 20 mg (n=148). Combination therapy was significantly more effective in reducing systolic blood pressure and pulse pressure than either monotherapy (p<0.0001). Significantly greater percentages of patients in the combination group compared with either monotherapy achieved blood pressure control (p<0.0001). Adverse events were low in all three treatment arms, with less peripheral edema in the combination group than in the amlodipine-treated group.

Therapy of obesity associated hypertension

There is a 50 % prevalence of obesity with arterial hypertension. This ratio can increase up to 80 %, depending on body mass index. Important pathogenetic origins are quantity of visceral body fat along with the activation of neuroendocrineum (sympathicus, renin-angiotensin system), an induction of insulin resistance with hyperinsulinemia, and a direct compression of the medulla by fat deposits in the kidneys, which results in hemodynamic changes and an increase in blood pressure.

The primary aim is a reduction in weight by means of a balanced diet and life style modification, which can be augmented by weight reducing medication.

• Orlistat lowers blood pressure and body weight simultaneously
• sibutramine accomplishes this only under certain circumstances.
  

Interestingly, blood pressure increases again over the course of 10 years following weight reducing surgical procedures, despite ongoing weight loss.

Antihypertensive differential therapy should be focused on pathophysiology and concomitant and target organ disease.

• Preferentially ACE inhibitors (alternatively angiotensin receptor blockers), in combination with low dose diuretics
• followed by calcium antagonists
• Beta blockers should be used if definite cardiac indications are present

Reference:
Dtsch Med Wochenschr. 2005 Nov 18;130(46):2645-50.

Office Blood Pressure measurements usually incorrect

Clinical Question:
How well do blood pressure measurements taken in the office correlate with a gold standard in-office measurement?

Bottom Line:
In this study, usual blood pressure readings in an office were frequently higher a standardized measurement, leading to incorrect labeling of blood pressure control in 1 of 5 patients.Health professionals should be aware of this potential difference when utilizing clinic-based BP values for making treatment decisions and/or assessing quality of care.

Reference:
How well do clinic-based blood pressure measurements agree with the mercury standard?
Kim JW, Bosworth HB, Voils CI, Olsen M, Dudley T, Gribbin M, Adams M, Oddone EZ.J Gen Intern Med. 2005 Jul;20(7):647-9.

Study Design:
Diagnostic test evaluation

Funding:
Government

Setting:
Outpatient (primary care)

Synopsis:
The researchers conducting this study compared the blood pressure measurements recorded during a visit to an internal medicine clinic with those obtained from the same patients by a trained research assistant. Using a convenience sample of 100 patients, most of whom were taking antihypertensives, the researchers measured blood pressure either before the clinic visit or immediately afterward, on average approximately 24 minutes within the time of the clinic reading. The researchers were carefully trained and performed all the measurements according to the book; proper cuff size, arm at heart level, patients resting for 5 minutes, air pressure released slowly. They used a mercury sphygmomanometer with a random zero, meaning that the blood pressure numbers they obtained on the patients were not real but had to be converted to the real number by subtracting a number that was unique to each measurement. This research tool is designed to prevent blood pressure readings to be read where the researcher thinks the number should be. The clinic blood pressure measurements were performed by the office nurse. Overall, the agreement between the measurements on individual patients was good, with an intraclass correlation coefficient of .91 (95% CI, 0.62 - 0.86). However, using the degree of agreement statistic, clinic-based measurements were 8.3 mm Hg systolic and 7.1 mm Hg diastolic higher than the standard. A possible clinical impact, due to misclassification of blood pressure, could have occurred in 21% of patients who had controlled blood pressures as measured by the researcher but were uncontrolled according to the clinic measurement. The degree of overestimation more commonly occurred when blood pressures were in the normal range.

Low cholesterol predicts death in elderly

Clinical Question:
Does a low cholesterol level predict mortality in the elderly?

Bottom Line:
Low cholesterol level is a robust predictor of mortality in the nondemented elderly and may be a surrogate of frailty or subclinical disease. More research is needed to understand these associations.

Reference:
Relationship between plasma lipids and all-cause mortality in nondemented elderly.Schupf N, Costa R, Luchsinger J, Tang MX, Lee JH, Mayeux R.J Am Geriatr Soc. 2005 Feb;53(2):219-26.

Study Design:
cohort (prospective) study

Setting:
Population-based

Synopsis:
The author investigated the relationship between plasma lipids and risk of death from all causes in nondemented elderly. Prospective cohort study was done in a Community-based sample of Medicare recipients, aged 65 years and older, residing in northern Manhattan. Two thousand two hundred seventy-seven nondemented elderly, aged 65 to 98; 672 (29.5%) white/non-Hispanic, 699 (30.7%) black/non-Hispanic, 876 (38.5%) Hispanic, and 30 (1.3%) other. Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-HDL-C, body mass index, and apolipoprotein E (APOE) genotype. clinical measures: neuropsychological, neurological, medical, and functional assessments; medical history of diabetes mellitus, heart disease, hypertension, stroke, and treatment with lipid-lowering drugs. Vital status measure: National Death Index date of death. Survival methods were used to examine the relationship between plasma lipids and subsequent mortality in younger and older nondemented elderly, adjusting for potential confounders. Nondemented elderly with levels of total cholesterol, non-HDL-C, and LDL-C in the lowest quartile were approximately twice as likely to die as those in the highest quartile (rate ratio (RR)=1.8, 95% confidence interval (CI)=1.3-2.4). These results did not vary when analyses were adjusted for body mass index, APOE genotype, diabetes mellitus, heart disease, hypertension, stroke, diagnosis of cancer, current smoking status, or demographic variables. The association between lipid levels and risk of death was attenuated when subjects with less than 1 year of follow-up were excluded (RR=1.4, 95% CI=1.0-2.1). The relationship between total cholesterol, non-HDL-C, HDL-C, and triglycerides and risk of death did not differ for older (>or=75) and younger participants (>75), whereas the relationship between LDL-C and risk of death was stronger in younger than older participants (RR=2.4, 95% CI=1.2-4.9 vs RR=1.6, 95% CI=1.02-2.6, respectively). Overall, women had higher mean lipid levels than men and lower mortality risk, but the risk of death was comparable for men and women with comparable low lipid levels.