Online Pharmacy, Canadian Pharmacy & Health Related News

Research supports growing belief that guidelines for prescribing statins should be expanded.

By Jeremy Cockerill | July 3, 2009

Research supports growing belief that guidelines for prescribing statins should be expanded.
HealthDay (6/30, Edelson) reported that a “meta-analysis of 10 trials involving more than 70,000 participants found that statin therapy reduced overall mortality by 12 percent, major coronary events by 30 percent, and strokes by 19 percent.” This “supports the findings of the JUPITER trial, reported last year, which noted 54 percent fewer heart attacks and 48 percent fewer strokes among people taking a statin who had normal cholesterol levels but high levels of C-reactive protein, a marker of inflammation, said Dr. Antonio M. Gotto, Jr., dean of Weill Cornell Medical College, a member of the international team reporting on the meta-analysis in the BMJ online.”

Angiotensin inhibition in the prevention of atrial fibrillation

By Jeremy Cockerill | July 3, 2009

Angiotensin II has been shown to play a role in the cardiac remodeling that contributes to AF in both human and animal atrial models. It promotes vasoconstriction, sodium and water retention, cardiac hypertrophy, and results in structural changes due to fibroblast stimulation and increased fibrotic tissue.

Thus, it seems logical that a RAS inhibitor would be useful in AF prevention.

In addition to translational and mechanistic studies, post hoc analyses involving RAS inhibitors performed on HF (SOLVD-enalapril, Val-HeFT-valsartan, CHARM-candesartan) and MI trials (GISSI-3-lisinopril, TRACE-trandolapril) all demonstrated a significant reduction in new-onset AF, and patients with left ventricular systolic dysfunction (LVSD) derived the greatest benefit.

Several hypertension trials have examined the occurrence of new AF. For example, secondary analysis of the LIFE study revealed that new-onset AF occurred in 6.8% of patients treated with losartan (Cozaar, Merck) compared with 10.1% of those randomized to atenolol (HR 0.67, 95% CI: 0.55-0.83; P<.001). Furthermore, in the VALUE trial, the occurrence of new onset AF (a prespecified secondary endpoint) in patients treated with valsartan (Diovan, Novartis) was 3.67% compared with 4.34% in patients treated with amlodipine (HR 0.84, 95% CI: 0.713-0.997; P=.045). Lastly, the recent ONTARGET study, which evaluated telmisartan (Micardis, Boehringer Ingelheim), ramipril or the combination in high-risk patients, assessed new-onset AF as a secondary endpoint, and no difference was detected.

Several metaanalyses evaluated the use of RAS inhibitors for AF prevention. Anand et al showed an 18% relative risk reduction in new-onset AF, with patients who had HF deriving the greatest benefit. In this analysis, ACE inhibitors (RR 0.75, 95% CI: 0.57-0.99) were more effective in preventing AF than ARBs (RR 0.81, 95% CI: 0.62-1.06). Healey et al also performed a metaanalysis with similar results, showing that RAS inhibitors reduced the risk of AF by 28% (95% CI: 15-40%, P=.0002); patients with impaired LV function benefited most. However, no difference was seen between ACE inhibitors (RRR 28%, 95% CI: 0.07-0.44, P=.01) and ARBs (RRR 29%, 95% CI: 0.16-0.40, P=.0002).

Prospective studies have also yielded positive outcomes. Ozaydin et al conducted a study (n=128) examining the use of an ACE inhibitor alone [lisinopril, n=80; cilazapril, n=7; ramipril and quinapril, n=4; perindopril (Aceon, Solvay), n=2; and fosinopril, n=1] and in combination with candesartan in postoperative cardiac patients. There was a 33% occurrence of AF in the control group, compared with the ACE inhibitor group (12%, P=.02) or the combination group (10%, P=.01).

GISSI-AF, the largest trial to date to prospectively assess the effect of RAS inhibition on AF prevention, was recently published in the New England Journal of Medicine. More than 1,400 high-risk patients with a prior history of AF were randomized to either valsartan or placebo. Primary outcomes were time to first recurrence of AF and the proportion of patients who had more than one recurrence over one year. After a one-year follow-up, valsartan did not show a reduction in recurrent AF (51.4% in valsartan group vs. 52.1% in the control group, and there was no difference in the time to first occurrence of AF, HR 0.97, 96% CI: 0.83-1.14; P=.83). Also, more than one AF recurrence was noted in 26.9% of valsartan-treated patients compared with 27.9% of the control patients (OR 0.89, 99% CI: 0.64-1.23; P=.34). As observed previously, although not statistically significant, in patients with HF, LVSD, or both, there was a trend toward benefit in the valsartan group (HR 0.81, 95% CI: 0.48-1.35; P=.41).

Although RAS blocking agents are routinely used in the management of many CV conditions including HF and ACS, current data do not support their use for the prevention of AF. The precise mechanism behind how RAS inhibitors can reduce the occurrence of AF is unclear, although it does appear that patients with impaired LVSD obtain better outcomes likely resulting from attenuation of cardiac remodeling. The robust GISSI-AF investigation failed to illustrate an overall benefit with valsartan. However, there are ongoing studies in high-risk populations, including those with diabetes and those who have undergone cardiac surgery that will further clarify the role of RAS inhibition in AF prevention.

Antoine Jenkins, PharmD, BCPS, is a Clinical Pharmacist, OSF St. Francis Medical Center, Peoria, Ill.

ACE, ARB Slow Retinopathy but Not Nephropathy in Type 1 Diabetes

By Jeremy Cockerill | July 2, 2009

Type 1 diabetes patients who start on renin-angiotensin blockers early may slow development of retinopathy by up to 70%, a clinical trial revealed.

But neither an angiotensin-receptor blocker (ARB) nor an ACE inhibitor significantly slowed progression of nephropathy over five years by any measure, Michael Mauer, MD, of the University of Minnesota in Minneapolis, and colleagues reported in the July 2 issue of the New England Journal of Medicine.

These findings challenge the widely accepted belief that inhibition of the renin-angiotensin system in patients with diabetes counteracts both early and advanced stages of nephropathy, according to an accompanying editorial.

Andrzej S. Krolewski, MD, PhD, of Harvard and the Joslin Diabetes Center in Boston, and colleagues commented in the editorial that numerous studies suggesting renal benefits were of short duration and focused primarily on urinary albumin excretion as a surrogate for kidney function.

But Dr. Mauer’s results shouldn’t have been entirely unexpected, they said.

Even the most influential trial supporting an effect on nephropathy — the Collaborative Study Group’s captopril (Capoten) trial — showed an effect on creatinine doubling time in advanced nephropathy but not in those with creatinine levels of less than 1.5 mg/dL, the editorialists noted.

So for a more rigorous look at renal effects of renin-angiotensin blockade in diabetes, Dr. Mauer’s group conducted the Renin-Angiotensin System Study (RASS), which followed patients for progression of the early histologic lesions of diabetic nephropathy seen on biopsy.

The trial included 285 patients with type 1 diabetes but normal albumin excretion and blood pressure levels. They were randomly assigned to receive losartan (Cozaar), enalapril (Vasotec), or placebo for five years.

Midway through the trial, the 50-mg daily dose of losartan and 10-mg daily dose of enalapril were doubled based on data from another trial.

For the primary endpoint, the change in mesangial fractional volume from baseline to five years was not significantly different for losartan or enalapril compared with placebo (+0.026 and +0.005 versus +0.016 units, P=0.17 and P=0.16, respectively).

Other secondary measures of biopsy-assessed renal structural changes, such as interstitial fractional volume, showed generally similar results.

The five-year cumulative incidence of microalbuminuria was actually higher with losartan than with placebo (17% versus 6%, P=0.01), but was similar between enalapril and placebo (4% versus 6%, P=0.96).

This “unexpected and unexplained” increase in microalbuminuria incidence needs further confirmation in a randomized controlled trial, the researchers cautioned.

“Nonetheless, careful monitoring of the albumin excretion rate is recommended if ARBs are prescribed to such patients,” they recommended.

But there were no differences in kidney function between groups as assessed by the glomerular filtration rate over the five years (declines of 6.6 to 8.9 ml per minute, P<0.002 for all three versus baseline).

For the retinopathy endpoint, progression of two or more steps on a 15-step diabetic retinopathy severity scale occurred in only 25% of patients who got enalapril and 21% of those who got losartan compared with 38% who got placebo (P=0.02 and P=0.008).

This 65% risk reduction with enalapril (odds ratio 0.35 versus placebo, 95% confidence interval 0.14 to 0.85) and 70% risk reduction with losartan (odds ratio 0.30 versus placebo, 95% CI 0.12 to 0.73) appeared to be independent of blood pressure effects and glycemia.

"The benefits of enalapril and losartan on diabetic retinopathy in the present study may represent direct effects on the eye," the investigators posited, but noted, "we cannot rule out effects of blood pressure on these diabetic retinopathy outcomes."

The inconsistency in retinopathy effects in this trial compared with the DIRECT series of trials with the ARB candesartan (Atacand) might reflect differences in sample size and the drugs and doses administered, the editorialists said. (See ARB May Retard Diabetic Retinopathy for Some Patients)

Dr. Mauer’s group cautioned about extrapolating between early and advanced stages of diabetic nephropathy and between type 2 and type 1 diabetes, “especially given the substantial differences in the relation of renal structure to albuminuria and the frequent presence of hypertension, obesity, and other risk factors for albuminuria in patients with type 2 diabetes.”

Likewise, the editorialists pointed to a variable strategy for these different populations:

Inhibition of the renin-angiotensin system should not be considered for normotensive patients with type 1 diabetes and normoalbuminuria.

Use of ACE inhibitors and ARBs should be questioned for microalbuminuria in patients with type 1 or type 2 diabetes, “since evidence of prevention of early decline in renal function is limited.”

Recognition of little chance of retinopathy benefit for patients with type 1 diabetes who have established retinopathy or for those with type 2 diabetes regardless of retinopathy status.

Dr. Krolewski’s group also cautioned that “further work is required before the strategy is used for retinopathy prevention in clinical practice,” including determination of the duration of therapy and subgroups that might not benefit.

Prescription eliminates urge to smoke

By Jeremy Cockerill | June 30, 2009

Area physician says more people try to quit when costs rise

Dr. Frances Bollinger, an internist with Hudson Headwaters Health Network, sees a familiar trend: When the price of a pack of cigarettes tracks upward, more of her patients decide they want to quit smoking.

Earlier this year, the federal excise tax on tobacco products saw its most dramatic increase in history — from 39 cents to $1.01 on a pack of cigarettes — as a means to raise revenue for an expansion of children’s health care. In addition, New York’s tobacco tax climbed $1.25 last year to $2.75.

A check of four area convenience stores shows the average price of a pack of Marlboro cigarettes at $7.68. A smoker consuming a pack a day will spend $53.76 per week, $215.04 per month and $2,795.52 per year.

“Smoking is such a risk-laden habit in terms of heart disease, COPD (chronic obstructive pulmonary disease) and lung cancer that it is frequently the No. 1 risk that you want them to reduce,” Bollinger said.

Susan Gates, 45, started smoking in high school 23 years ago when “everybody” was doing it. She tried quitting cold turkey four times, but this method left her very anxious.

“My kids thought I was snapping at them all the time,” she said.

The longest stretch she went without a cigarette was between four and five months. But she was always drawn back because her husband smokes.

“(The desire) was there,” she said.

More than a year ago, Gates heard about the prescription medicine Chantix and thought she’d give it a try.

Chantix, the trade name for the drug varenicline, works by targeting the nicotine receptors in the brain that involve the pleasurable feelings one gets from smoking.

The medicine binds to the receptors and blocks them, preventing a smoker’s typical response to nicotine. As a result, a smoker should get less satisfaction from each successive cigarette to the point that he or she won’t want another.

Also, by releasing dopamine in the brain, Chantix inhibits the cravings from nicotine withdrawal, according to the Web site www.healthline.com.

After a rocky start — Gates quit the drug after a few weeks because of nausea, a common side effect — she made another attempt.

Gates received a one-month starter pack and went back to see her doctor for a repeat prescription.

After taking a pill twice a day, Gates was told she could continue to smoke as much as she wanted. She gradually lost her desire to smoke so that by the end of three weeks, she was only smoking three or four cigarettes per day, down from her usual pack of 20.

After being on Chantix for four months, she felt she could stop taking the medicine and quit smoking.

That was 13 months ago.

“I have no desire. It takes that urge right away,” Gates said.

The treatment wasn’t without side effects, though.

She experienced nausea for about a half hour after ingesting each pill, and she had nightmares, which subsided after about a month or two. Gates also gained 25 pounds, but because she was very thin as a smoker, this didn’t bother her.

Gates now only sees her doctor for regular check ups.

Besides the common side effects like mild nausea and nightmares, there are warnings of erratic behavior and suicidal thoughts.

“The FAA is not allowing pilots to use it because of maybe some visual disturbances. They’re sort of still working their way through that,” Bollinger said.

Chantix should not be used for those with psychiatric or behavioral issues, Bollinger said.

Still, Bollinger has been impressed with success she has seen locally with Chantix.

She recommends patients supplement pharmacologic therapy with physician counseling and behavior modification. Behavior therapy alone has the lowest success rate, she said, but the effectiveness of the program will increase “two fold” alongside nicotine replacement medicine, which provides nicotine without the tar and carcinogens.

Other pharmacologic therapies available include the anti-depressant Wellbutrin.

However, any method has to be suited to the patient’s individual needs, Bollinger said.

The more attempts a person makes to stop smoking, the closer he will become to succeeding because he has learned new skills, she continued.

“Smoking is a risk factor for disease that we can modify,” she said. “Your provider can work to come up with a method that hopefully will work for you. There are different options. Don’t give up.”

The truth about generic drugs

By Jeremy Cockerill | June 25, 2009

By Jessica Shambora

Health care reform is front and center — and an insanely complicated issue. When someone talks about simple solutions, it’s time to listen. So we were all ears when Jacqueline Kosecoff, CEO of Prescription Solutions, came by Fortune last week and sat down with us to talk about generic drugs.

Up in New York City after a day on Capitol Hill, Kosecoff was eager to talk about how her UnitedHealth Group (UNH) unit, which is a Prescription Benefits Manager (PBM) accounting for $13 billion of UnitedHealth’s $81 billion in revenue, can save the system millions of dollars. Her claim is based on a new study, released by Prescription Solutions this week, that shows a big void in consumer understanding about generics — what they are and what savings they bring.

You may already know that generics are identical to brand-name drugs, but the study found that nearly one-third of Americans either don’t know or don’t believe that. Among people who do not take generics, only 58% say it’s because there isn’t a generic alternative available. Moreover, two-thirds of survey respondents don’t realize that brand-name drugs typically cost 50-70% more than generics.

Says Kosecoff: “Many Americans erroneously believe that the most expensive drug is always the most effective drug.”

Generics have already saved the health-care system $734 billion over the past decade, according to market researcher IMS Health. Koseocoff says that a 1% uptick in generic use equates to 1.7% savings for payers, such as employers. And consumers enrolled in its drug plans typically save $20-60 per prescription by switching.

This is why Kosecoff is pushing generics hard: She talks about a “triple win” for consumers, for payers, and for Prescriptions Solutions. If her unit delivers more value, it’s likely to get more volume and make more money. And it’s all about value these days. The study also showed stretched consumers have been cutting back on prescriptions: 27% of survey respondents said that they delayed filling, didn’t fill or didn’t take a drug in order to save money.

As the generic market grows, the biggest loser is Big pharma, whose brand-name drugs inevitably lose share. Through 2013, $134 billion in branded drugs are at risk from generic competition in eight key drug markets, according to IMS Health. Popular drugs like Pfizer’s (PFE) Lipitor, GlaxoSmithKline’s (GSK) Valtrex, and Boehringer Ingelheim’s Flomax are among the drugs with patents set to expire fairly soon.

As Kosecoff works to spur that generics market — and cut costs for Prescription Solutions’ customers — she’s pushing another item on her agenda: cheaper alternatives for biologics. These drugs, such as Amgen’s (AMGN) arthritis drug Enbrel and Abbott’s (ABBT) Humira, also for arthritis and for Crohn’s Disease, are the fastest-growing area of pharmaceuticals — a market expected to hit $90 billion this year, up from $40 billion in 2005. But generics don’t exist for biologics, which are made from living organisms rather than the small molecules of conventional pharma.

Kosecoff wants to change that. And she’s calling for Congress to help make it happen. ”A regulatory approval pathway for follow-on version of thes biologic drugs must be created,” she says.