Bisher AKIL, MD

Archive for the ‘Heart’ Category

HIV Related High Lipids is Difficult to Treat

In Heart on April 1, 2009 at 12:30 am

Dyslipidemia (abnormal lipids in blood) is common in HIV-infected patients, but treatment outcomes are often unsatisfactory. In this study from Kaiser Permanente in California, investigators compared responses to lipid-lowering therapy between 829 HIV-infected patients and 6941 uninfected controls, all with laboratory evidence of dyslipidemia. The HIV-infected patients had significantly smaller LDL (low density lipoprotein) declines in response to statin therapy than their HIV-negative counterparts (reduction, 25.6% vs. 28.3%); within the HIV population, pravastatin (Pravachol®) was less effective than other agents (simvastatin – Zocor®, lovastatin – Mevacor®, or atorvastatin- Lipitor®). Response to fibrate therapy (gemfibrozil – Lopid®) was also worse among HIV-infected patients, particularly those receiving PIs. Three cases of rhabdomyolysis occurred in the HIV-infected group versus one in the control group; laboratory abnormalities occurred in fewer than 5% of those with HIV infection.

Abacavir and Risk for Heart Disease

In Heart on March 23, 2009 at 2:04 pm

In February 2008, findings from the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study indicated that the incidence of myocardial infarction increased nearly two-fold with recent (less than 6 month) use of abacavir. Subsequently, a retrospective analysis from the SMART (The Strategies for Management of Antiretroviral Therapy) study revealed similar results. In the ensuing year, data from various studies fell on both sides of the subject. This year at the 16th Conference on Retroviruses and Opportunistic Infections (CROI), four different studies were presented, adding more to the controversy:
1. An updated analysis from the DAD Study, involving >178,000 person-years of follow-up, confirmed that recent abacavir use was strongly associated with increased risk for myocardial infarction (MI), whereas cumulative exposure was only modestly associated with myocardial infarction.
2. A case-control study from the French Hospital Database group, involving 289 MI cases and 865 controls, showed that recent, short-term use (<1 year) of abacavir was significantly associated with MI risk
3. In the STEAL Study from Australia, 357 patients with viral loads <50 copies/mL who were HLA B5701–negative had the NRTIs in their current regimens switched to either abacavir/3TC (Epzicom) or tenofovir/FTC (Truvada). At week 96, abacavir/3TC was associated with significantly more cases of serious CVD (8 vs. 1)
4. In contrast to these data, a pooled analysis of five ACTG studies, all conducted in patients initiating antiretroviral therapy (ART), showed no evidence of a link between recent abacavir use and cardiovascular outcomes.
The mechanism of this association was also a subject of speculation and more controversy: The manufacturer-sponsored, randomized HEAT Study, 96-week changes in inflammatory markers (C-reactive protein and interleukin-6) and endothelial activation markers (vascular cell adhesion molecule-1) did not differ significantly between patients who started ART with abacavir/3TC and those who started with tenofovir/FTC. Similar null results were seen in biomarker analyses from the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study and also from ACTG 5095. However, two small studies did suggest that abacavir use was associated with impaired brachial dilatation and increased platelet aggregation.
In reviewing the data from the conference, Dr. Peter Reiss (Associate Professor of Medicine, Academic Medical Center at the University of Amsterdam, and a member of the DAD Study Group), he noticed that studies showing a relationship between abacavir and heart disease had patients that tend to be 7-10 years older than other studies and are usually receiving antirotriviral therapy (ART) with viral suppression.
Comments: This association remains unclear. Furthermore there is no clear etiology ( or more likely several etiologies). People with risk for coronary artery disease (smoking, over 45 years of age, male,…etc) need be evaluated carefully for the choice of medications. What is clear: no one treatment fits all, and the risk for heart disease should be assessed carefully in each individual. Treatment for underlying problems (such as hypertension, hyperlipidemia, obesity, smoking,…etc) much be addressed and treated as aggressive as one treats HIV itself_ BA.

Treatment Induced Changes in HDL , LDL and Heart Disease

In Heart on March 22, 2009 at 11:06 pm

High-density lipoprotein (HDL) cholesterol level is associated independently and inversely with coronary heart disease risk. However, evidence that treatment-mediated increases in HDL cholesterol levels lower risk for heart disease is lacking. In analysis of 108 randomized trials (Briel M et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: Systematic review and meta-regression analysis. BMJ 2009 Feb 16; 338:b92.), involving nearly 300,000 patients, investigators assessed whether changes in HDL and Low -density lipoprotein (LDL) as a result of medical treatment was associated with changes in the risk for heart disease.
All but five trials involved lipid-modifying drugs. After adjustment for changes in LDL cholesterol levels related to treatment and drug class, no associations were noted between treatment-mediated changes in HDL cholesterol levels and all-cause death. However, changes in LDL cholesterol levels were associated with significant outcomes: For a 10 mg/dL reduction in LDL cholesterol level, relative risks were lowered for all-cause death by 4.4%, for coronary heart disease-related death by 7.2%.
Comments: the good news is that is the LDL is lowered using medications, there is clear and significant benefit; on the other hand, changes in HDL did not seem to make a difference, in this analysis. This analysis may not reveal hidden benefits for increasing HDL, but it makes it clear that the goal of treatment should be lowering LDL _ BA

Vitamin C & E: do they prevent heart disease?

In Heart on March 17, 2009 at 11:59 pm

Data have suggested possible benefit from antioxidants, especially vitamin C &E in preventing cardiovascular events. However, this benefit has never been confirmed. The Physician’s Health Study II (PHS II) trial was designed to answer this question. The data were presented by Dr. J. Michael Gaziano at the American Heart Association Annual Scientific Sessions, New Orleans, November 2008. The study was placebo controlled, randomized, blinded, parallel and factorial. It screened 273,360 and enrolled: 14,641 male US physicians with mean follow-Up of 8 years and mean age: 64.3 years. Patients were randomized in a 2 x 2 x 2 x 2 factorial trial to either vitamin E (400 IU synthetic α-tocopherol) or placebo every other day, vitamin C (500 mg synthetic ascorbic acid) or placebo daily, multivitamin (Centrum Silver) or placebo, and beta-carotene (50 mg of Lurotin) or placebo every other day. A total of 14,641 healthy males were randomized, 3,656 to active vitamins E and C, 3,659 to active vitamin E and placebo vitamin C, 3,673 to placebo vitamin E and active vitamin C, and 3,653 to placebo vitamins C and E. Baseline characteristics were fairly similar between the four groups. About 61% exercised at least once every week, about 44% were past or current smokers, 77.4% were on aspirin, 42% had a history of hypertension, 36% had a history of hypercholesterolemia, 6% had a history of diabetes, and about 5% had a self-reported history of cardiovascular disease. Compliance was about 72% at 8 years.
Vitamin E: There was no difference between patients receiving vitamin E or placebo in the incidence of major cardiovascular events (8.5% vs. 8.5%, hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.90-1.13, p = 0.86). There was also no difference in the incidence of myocardial infarction (MI) (3.3% vs. 3.7%, p = 0.22), stroke (3.2% vs. 3.1%, p = 0.45), congestive heart failure (4.0% vs. 4.0%, p = 0.80), or all-cause mortality (11.5% vs. 11.2%, p = 0.15). However, there was a significant increase in the risk of hemorrhagic stroke in the vitamin E arm (0.53% vs. 0.31%, HR 1.74, 95% CI 1.04-2.91, p = 0.04).

Vitamin C: There was no difference between patients receiving vitamin C or placebo in the incidence of major cardiovascular events (8.4% vs. 8.6%, HR 0.99, 95% CI 0.89-1.11, p = 0.91). There was also no difference in the incidence of MI (3.5% vs. 3.4%, p = 0.65), stroke (3.0% vs. 3.4%, p = 0.21), or all-cause mortality (11.7% vs. 11.0%, p = 0.16).


The results showed  that neither vitamin C nor vitamin E supplementation is associated with a reduction in major cardiovascular outcomes, as compared with placebo, although vitamin E may be associated with a slightly higher incidence of hemorrhagic stroke, compared with placebo.

Comments: No women were enrolled in this study which limits its benefit; questionnaire were used to assess the results. These may make the results a bit weaker, but they are still valid. Next time you decide to buy vitamins, make sure you are buying them for a good reason, otherwise save your money.BA