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Quitting smoking reduces heart disease risk despite weight gain

By Jeremy Cockerill | February 5, 2010

Source: MedWire News

Stopping smoking can lead to weight gain and a worsening in some cardiovascular risk factors, Japanese research suggests, but it still markedly reduces an individual’s estimated risk of coronary heart disease.

Notably, levels of high-density lipoprotein (HDL) cholesterol increased after quitting smoking, although total cholesterol levels also increased.

The team analyzed survey information from 1995 Japanese male smokers who had participated in an occupational health promotion study.

Participants had cardiovascular risk factors measured at baseline and over a 4-year period. Overall, 985 men continued to smoke during follow-up and 117 successfully quit for at least 6 months during this period.

Men who quit smoking experienced an average weight gain of 2.4 kg during the 4 years of follow-up, compared with 0.5 kg in continuing smokers.

Men who successfully stopped smoking for at least 6 months also had a worsening in several cardiovascular risk factors compared with continuing smokers.

These included systolic and diastolic blood pressure, total cholesterol, triglycerides, and fasting blood sugar levels.

However, HDL-cholesterol levels improved significantly more in those who had quit for at least 6 months than in continuing smokers, with rises of 3.7 mg/dl (0.096 mmol/l) versus 0.2 mg/dl (0.005 mmol/l).

When the overall instantaneous incidence risk of coronary heart disease prior to smoking cessation was assumed to be 1, the estimated risk for those who had quit smoking for at least 6 months was significantly reduced at 0.76.

This occurred despite the weight gain, and was mainly due to having quit smoking.

“These results suggest that coronary risk reduction after smoking cessation may be further decreased by inhibiting weight gain,” Unai Tamura (University of Yamanashi, Japan) and colleagues report in the Journal of Atherosclerosis and Thrombosis.

“It is necessary to disseminate to the public that many benefits attained by stopping smoking, despite the associated weight gain,” they add.

Study shows protease inhibitors more forgiving of missed doses, even when treatment out of date

By Jeremy Cockerill | February 4, 2010

Less than perfect adherence to HIV treatment regimens significantly increases the risk of resistance developing to drugs in the NNRTI and NRTI classes, investigators report in the January 28th edition of AIDS.

Poor adherence to boosted protease inhibitors did not, however, involve a significant risk of resistance.

Adherence is the single most important factor under a patient’s control affecting the success of their antiretroviral therapy. Poor adherence to treatment has been linked to increases in viral load and the development of drug-resistant virus.

However, the relationship between adherence and resistance differs between classes of antiretroviral drugs. A better understanding of the relationship between drug classes, adherence, and the risk of resistance can assist in the design of treatment strategies.

But most studies looking at the connection between adherence and the risk of resistance for specific classes of drugs have either been small or had a short period of follow-up.

Therefore investigators from the US CPCRA FIRST 058 study conducted a prospective analysis involving over 900 patients starting antiretroviral therapy for the first time. The patients had several years of follow-up data available for analysis.

A total of 457 individuals who started a regimen including a protease inhibitor, and 446 patients who started treatment that included a non-nucleoside reverse transcriptase inhibitor (NNRTI), were included in the study. Both groups of patients also took two nucleoside reverse transcriptase inhibitors (NRTIs).

Recruitment to the study was conducted between 1999 and 2002. This meant that many patients took drugs that are no longer recommended for first-line use. In particular, almost two-thirds of patients taking a protease inhibitor were taking nelfinavir (Viracept), and although 21% took a ritonavir-boosted protease inhibitor, most (13%) were treated with ritonavir-boosted indinavir (Crixivan). The most commonly used NNRTI was efavirenz (Sustiva), a drug which remains the cornerstone of initial antiretroviral regimens.

Of the patients taking a protease inhibitor, 71% experienced a rebound (above 1000 copies/ml) in their viral load a median of 1.2 years after starting treatment.

At the time of virological failure, 8% of these patients had resistance to a protease inhibitor and 26% had resistance to an NRTI. Two-class resistance was present in 9% of individuals.

Viral load rebounded in 59% of those taking an NNRTI, and this occurred within a median of three years of starting treatment. A quarter of these patients had resistance to NNRTIs and 14% had NRTI resistance. Resistance to both NNRTIs and NRTIs was found in 11% of patients.

No association was found between adherence and the development of resistance to protease inhibitors.

However, for patients taking an NNRTI, each 10% reduction in adherence levels was association with a 20% increase in the risk of resistance (HR = 1.2; 95% CI, 1.1 – 1.3).

Further statistical analysis that controlled for potentially confounding factors confirmed that adherence levels were not associated with the development of resistance to protease inhibitors.

For patients taking an NNRTI, however, good, but imperfect adherence between 80-99% was associated with a 130% increase in the risk of resistance (HR = 2.3; 95% CI, 1.4-3.7). The risk of resistance was even higher at adherence of 79% and below (HR = 6.5; 95% CI, 3.9-10.7).

Regardless of whether treatment was based on a protease inhibitor or an NNRTI, lower levels of adherence were associated with resistance to NRTIs. The risk of resistance to this class of drugs was especially associated with adherence between 80-99%.

“The data presented here represent one of the largest studies with the longest duration of follow-up to assess class-specific adherence-resistance relationships”, write the investigators.

They note, “no association between cumulative adherence and protease inhibitor resistance was found.” However, “for NNRTIs and NRTIs, we found a significant association between lower levels of cumulative adherence and resistance at initial virological failure.”

The researchers conclude, “in a population initiating antiretroviral therapy, the higher the level of cumulative adherence, the better the outcomes. Excellent adherence and full virological suppression remain the goal of antiretroviral therapy.”

“The message to HIV-infected individuals should be clear”, write the investigators, “complete virological suppression remains the goal of antiretroviral therapy. The best way to achieve complete virological suppression is to optimize adherence to all components of multidrug antiretroviral therapy.”

However, the investigators believe that their findings could “help provide the foundation for rational design of medication combinations and regimen sequencing to improve the longevity of currently available therapies in the era of HIV as a chronic illness.”

Metformin plus lifestyle changes may help lower obese teens’ weight.

By Jeremy Cockerill | February 4, 2010

Metformin plus lifestyle changes may help lower obese teens’ weight.
HealthDay (2/1, Dotinga) reported that, according to a study published in the February issue of the Archives of Pediatrics & Adolescent Medicine, “metformin plus lifestyle changes might play a role in obesity treatment.” Researchers randomized “77 fat adolescents, aged 13 to 18″ to placebo or to “a daily dose of 2,000 milligrams of metformin XR.”

WebMD (2/1, Warner) reported, “The results showed that the BMI of teens who received metformin in addition to lifestyle changes decreased 0.9 after 48 weeks’ study, compared to a 0.2 increase in the placebo group,” a difference that investigators “say…persisted for up to six months after” participants “stopped taking the drug.”

MedPage Today (2/1, Smith) reported that after “nearly two years of treatment and follow-up, the drug was associated with a statistically significant drop in body mass index,” but “appeared to have no effect on many other aspects of obesity, including fat distribution and insulin resistance.”

US healthcare spending saw largest one-year increase last year.

By Jeremy Cockerill | February 4, 2010

CMS released a report Wednesday in the journal Health Affairs that showed healthcare spending continued to grow in the US last year, and now constitutes 17.3% of the country’s GDP. Most major newspapers covered the story. The Washington Post (2/4, A7, Brown) reports, “Healthcare spending in the United States grew last year despite a contracting economy,” according to the CMS numbers. The 1.1% increase “in 2009 compared with 2008″ is “the largest one-year increase since at least 1960.” The government estimates that by 2019, “healthcare spending will be $2 trillion higher than it is now, it will represent 19.3 percent of the economy, and the government will pay 52 percent of it.”

The Wall Street Journal (2/4, A1, Landers) reports on its front page that in 2011 government programs are predicted to take up more than half of the country’s healthcare spending.

The Los Angeles Times (2/4, Levey) calls the report “a stark reminder of growing costs.” But, the increases, “driven in part by surging spending in Medicare and Medicaid, and the bleak projections for the future do not take into account changes that may come if Democrats revive their healthcare overhaul legislation.”

For 2009, the New York Times (2/4, A18, Pear) explains, “A major factor in the growth of health spending was the increase in Medicaid enrollment and Medicaid spending as a result of rising unemployment. As people lost jobs, they lost private insurance, and many turned to Medicaid.”

Christopher Truffer of Medicare’s Office of the Actuary, who authored the report, noted “This is certainly a very steep rate of growth,” USA Today (2/4, Fritze) reports. The figures are “the latest indication of the nation’s mounting medical expenses and it comes as Congress has stalled on President Obama’s proposal to revamp the healthcare system.”

The AP (2/4, Alonso-Zaldivar) calls the report “a reality check in the debate over Obama’s healthcare plan, which has been dominated by disagreements over how large a role government should play.” CMS’ Chief Actuary Richard Foster “said the recession has only worsened the two stubborn problems facing the US healthcare system: lack of insurance coverage and high costs.” He said, “All that argues that some form of healthcare reform is a good idea.”

No platelet aggregation rebound seen with discontinuation of clopidogrel.

By Jeremy Cockerill | February 1, 2010

MedPage Today (2/1, Bankhead) reports that “no evidence of a platelet aggregation rebound occurs with abrupt discontinuation of clopidogrel (Plavix) in patients undergoing percutaneous coronary intervention (PCI),” according to a study published in the Journal of the American College of Cardiology. Researchers found that “values for adenosine diphosphate (ADP)-induced platelet aggregation did not differ significantly between patients whose clopidogrel therapy was withdrawn abruptly and those in whom clopidogrel was tapered before discontinuation.” The investigators also found that “tapering of clopidogrel does not lead to lower platelet aggregation values after clopidogrel withdrawal.”