A Pitched Battle in Cardiovascular Drug Marketing

Mature product franchises and mixed clinical outcomes have not dissuaded pharma companies from expending marketing resources for cardiovascular disease treatment


Cardiovascular disease (CVD) and cancer have been the top killers in the industrialized world for years. But while the two are neck-and-neck, so to speak, for younger populations, CVD is the far-and-away primary cause of death for the elderly. Until recent decades, cancer used to be an event (it is now on its way to a type of chronic disease), but CVD has been mostly a chronic condition for patients for time immemorial (Fig. 1).

These disease state parameters, in turn, define the challenges and opportunities for the pharma industry in addressing CVD. The diseases that make up CVD (coronary artery disease, or CAD, stroke, cardiac arrest, hypertension, heart failure are the main ones) affect millions of people, creating instant blockbuster opportunities for successful treatments. So much is known about CVD that the ways to prevent, or minimize, its progression have long been practiced: drugs that reduce cholesterol in the bloodstream (and resulting plaque in arteries); anti-hypertensives to lower blood pressure; blood thinners to minimize stroke.

The potential for pharmaceutical intervention in CVD is further defined by the lifestyle issues of populations, and by the availability and aggressiveness of the medical professions to intervene directly in heart disease, through bypass surgery, angioplasty and other surgical repairs, up to and including heart transplants (of which there were about 2,200 in 2006, according to NIH).

The lifestyle factors in CVD are well known—eat right, exercise, don’t smoke—but industrialized societies have been contending with them with less than total success for so long that the care for CVD patients is itself a part of the pharmaceutical industry’s approach, opening the door for patient adherence programs (see p. 26), and for treatment of the conditions that lead to heart disease (obesity or smoking cessation, among others).

Heart disease earned the moniker “the silent killer” because it’s both chronic and asymptomatic in so many patients. This not only makes it particularly vexing to treat successfully, but creates unique challenges for pharma marketers, in terms of how best to structure the most effective outreach and support programs for both patients and physicians. “In many other disease areas, patients experience symptoms, so when they take their medication they often feel relief. But this is not the case for many cardiovascular conditions,” says Graeme Green, PhD, an analyst at market-research firm Decision Resources (Waltham, MA).

“So often, patients go to the doctor feeling okay, are told they’re sick, start taking medications to treat a problem they didn’t know they had, and end up feeling worse, either physically (because of side effects) or psychologically (because they’re reminded that they are sick and may be facing their own mortality),” adds Jay Bolling, president of Roska Healthcare Advertising (Montgomeryville, PA).

Since the onset and progression of high cholesterol, hypertension and other precursors of heart disease are directly impacted by the choices we make every day— choices related to diet and exercise, smoking, salt and alcohol intake — “patient behavior plays a huge role in managing so many CV diseases, so you have to develop outreach that engages or encourages patients to get more skin in the game,” says benefit consultant F. Randy Vogenberg, RPh, PhD, chief strategic officer for Employer-Based Pharmaceutical Strategies LLC (EPS) and principal for the consultancy Institute for Integrated Healthcare (IIH; Sharon, MA).

“Getting a diagnosis of high cholesterol or high blood pressure doesn’t feel like getting a diagnosis of cancer because patients just don’t feel like they’re staring down the gun barrel at their own mortality — but they should,” concludes John Earl, PhD, director, cardiovascular, at Decision Resources.

CV landscape
The total estimated direct and indirect cost of CVD in the U.S. was $448.5 billion last year, according to 2008 statistics from the American Heart Association (AHA; Washington, DC). This includes direct health expenditures (i.e., the cost of physicians and other professionals, hospital and nursing home services, medications, home health care and other medical durables) and indirect costs from lost productivity resulting from morbidity and mortality (Fig. 2).

(By rough comparison, the total cost of all cancer and benign neoplasms in the previous year [2007] was $219 billion [$89 billion in direct costs, $18 billion in morbidity indirect costs and $112 billion in mortality indirect costs], according to the National Heart, Lung and Blood Institute of NIH.)

Given the fact that heart disease remains the number one killer of both men and women in the U.S. and elsewhere, drug makers, insurers, employers, doctors and others are working to ramp up the tone and content of their outreach efforts, to ensure that undiagnosed patients are made aware of their healthcare problems, and patients who are diagnosed view their life-threatening conditions as more than just a nuisance.

Meanwhile, considering what’s at stake both financially and clinically, it’s a dog-eat-dog world among the pharma giants, who are constantly working to not only develop improved therapeutic agents, but to both demonstrate the clinical advantages of their existing drugs over their competitors’ branded products (in an effort to dominate each of the various CV sub-sectors), and to use all means necessary to hang on to market share as wave after wave of patent expiries continues to rock the CV boat.

Other factors continue to complicate the picture in the CV market. Specifically, over the past year or two, many of the leading CV blockbuster drugs have courted controversy for a variety of reasons, and several eagerly anticipated CV agents in the developmental pipeline — drugs that were already being anointed potential blockbusters — have failed to gain FDA approval.


The pharma care contribution
In 2007, the global market for CV drugs, devices and diagnostics was an estimated $119.8 billion (up from $111 billion in 2006) and that figure is expected to reach $192.4 billion by 2012, (9.9% CAGR), according to BCC Research (Norwalk, CT). Roughly $82.4 billion of the 2007 total went for CV drugs, and this number is projected to reach $121.6 billion by 2012.

Worldwide, the top ten brands in the CV market enjoyed 2007 sales of nearly $47 billion (Fig. 3), according to Decision Resources, and this doesn’t account for sales of generic alternatives that are available in many of these categories (the impact of generics is discussed below).


In the U.S., four of the top ten therapeutic classes of drugs prescribed in the U.S. in 2007 (again, by the number of dispensed prescriptions) — lipid regulators (for lowering cholesterol), ACE inhibitors, beta blockers, and calcium channel blockers (all anti-hypertensives, for lowering high blood pressure) — are for treating CV conditions, according to IMS Health Plymouth Meeting, PA).


Similarly, four of the top 10 individual drugs prescribed in 2007 (by the number of dispensed prescriptions) were for treating CV conditions — lisinopril, an ACE inhibitor for high blood pressure, the anti-cholesterol drugs Lipitor (atorvastatin) and simvastatin (the generic form of Zocor), and atenolol, a beta blocker for high blood pressure.


Market trends
Overall, the CV market is fairly mature, with little overall change in total market value forecast over the next seven years, says Green of Decision Resources, who notes that the impact of rolling patent expiries in this sector is expected to be buffered by sales associated with promising new agents that are expected to become available in the near term. Three drug categories dominate the CV market: The anti-dyslipidemics (to modify cholesterol levels), the anti-hypertensive agents (to lower blood pressure), and the anti-thrombotic agents (blood thinners).

Cholesterol-lowering anti-dyslipidemics
Today, if your cholesterol levels are high, you’re not alone. According to the AHA, more than 106 million American adults have high cholesterol.

Statins (HMG-CoA reductase inhibitors) are considered the drug of choice for treating high cholesterol, with bile acid sequestrants, fiber acid derivatives and nicotinic acid bringing up the rear. In 2007, the global market for drugs used in the management of cholesterol is currently valued at around $34 billion.

“The loss of market exclusivity for Merck’s Zocor (simvastatin) and Bristol-Myers Squibb’s Pravachol (pravastatin sodium) in 2006 dealt a serious blow to the overall market value for branded statins,” says Nikhil Mehta, a senior analyst at Decision Resources, who notes that the more-recent introduction of the newer anti-cholesterol agents Crestor (rosuvastatin calcium) from AstraZeneca and the Merck/Schering-Plough combination pill Vytorin (ezetimibe/simvastatin) mentioned above has helped to buffer those losses.

Anti-hypertensives
When it comes to high blood pressure (hypertension), nearly a third of all white Americans now have high blood pressure, according to AHA. The situation is more dire for the African-American community, where nearly half of all black adults (42.6% of men, and 46.6% of women) are so afflicted.

According to a study conducted by the Tulane University School of Public Health (Lancet 2005, 365:217-23), and cited in the latest AHA statistical roundup, the prevalence of hypertension in the U.S. is expected to soar to 1.56 billion by 2025.

In the anti-hypertensive space, Pfizer’s calcium-channel blocker Norvasc (amlodipine besylate) was a huge seller for many years — with peak U.S. sales in 2006 of $4.9 billion — until a generic alternative became available several years ago. Following expiry of the last U.S. patent, sales declined in 2007 to U.S. $3 billion, as multiple generics penetrated the market.

“We’re seeing some growth in this space driven primarily by the angiotensin II antagonist drug class, from which the Novartis Diovan (Valsartan) franchise is key,” says Green from Decision Resources.

Novartis’ Diovan/Co-Diovan (valsartan) took over as market leader in 2007, with U.S. sales of $5.0 billion, an increase of 18.7% over 2006. Merck’s Merck’s Cozaar/Hyzaar (losartan potassium and losartan potassium with hydrochlorothiazide), an anti-hypertensive in the angiotensin II receptor antagonist class, ranked second, with sales amounting to $3.4 billion, a 5.9% increase over 2006.

When it comes to reducing blood pressure, it’s common practice for patients to take two or more anti-hypertensives—such as beta blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and andrenergetic blockers — to benefit from their different-yet-syngergistic mechanisms of action. To reduce the number of blood pressure pills a patient must take, several drug companies are developing combination pills, which combine two proven antihypertensives in a single, fixed-dosage pill. [This is similar — but not identical — to parallel efforts to develop dual-therapy “polypills” that combine two different types of drugs. Such an example would be Pfizer’s Caduet, which combines the company’s cholesterol-lowering drug Lipitor (atorvastatin) with its calcium channel blocker anti-hypertensive Norvasc (amlodipine).]

The ability to combine two proven anti-hypertensives in a single, fixed-dose pill offers several potential advantages, including improved outcomes, reduced side effects, lower costs, easier administration (by reducing the need for periodic titration to maintain optimal dosing rates), and increased patient adherence. And in some cases, it enables the creation of a novel product that may help to extend market exclusivity, protecting the aging franchise from generic competition.

One example is Novartis’ recently launched Exforge, which combines two branded anti-hypertensives in a single pill — the calcium channel blocker amlodipine (whose branded equivalent is Pfizer’s Norvasc) with Novartis’ Diovan (valsartan; an anti-hypertensive in the angiotensin II receptor antagonist class).

“Everyone generally agrees that taking one pill once a day is easier, but we will need to see data around better therapeutic outcomes and better compliance tied back to that,” says Brian Lasky, global therapy lead for cardiovascular, metabolism and nephrology for IMS Consulting (Wyomissing, PA). “From an insurance perspective, polypills are seen as a mixed bag,” he says. “Some are seen as true advances, but others are seen as a way to prop up branded sales when generic options exist.”

Anti-coagulants/Anti-thrombotics
While both anti-dyslipidemics and anti-hypertensives are well-established and mature CV drug classes that are only forecast to experience modest growth over the next five years, the analysts at Decision Resources are anticipating more robust growth in the anti-thrombotic sector. Anti-thrombotic drugs act by blocking platelets (anti-platelets) or coagulation (anti-coagulants), and are prescribed to prevent — or treat — blood clots. Thrombolytic agents break up blood clots that have already formed.

Plavix (clopidogrel) from Sanofi-Aventis/BristolMyers-Squibb is the leading oral anti-platelet agent, with nearly $4 billion in U.S. sales in 2007, and nearly 93% of the U.S. market share, by total prescriptions dispensed that same year.

In the anti-coagulant market, several newer oral agents are near commercialization, and once they become available, they are expected to go head-to-head with several of the leading blood-thinning agents, including oral Coumadin (Bristol-Myers Squibb’s version of warfarin sodium) and injectible heparin, and Lovenox (enoxaparin sodium injection, from Sanofi Aventis) — drugs whose names are practically synonymous with blood thinning.

Three to watch, according to Decision Resources analysts, are Xarelto (rivaroxaban) from Bayer and Johnson & Johnson and Pradaxa (dabigatran etexilate) from Boehringer Ingelheim (both of which are already available in Europe), and apixaban (from Pfizer/Bristol-Myers Squibb). There are six or seven similar oral agents working their way through the development pipeline as well.

Lasky of IMS notes that prasugrel (which will be marketed as Effient) by Eli Lilly and Daiichi Sankyo is another one to watch in this category, especially because of the FDA advisory committee’s unanimous decision in favor of approval. “A 2007 study showed that prasugrel is more effective than the popular blood thinner Plavix in reducing heart attacks but increased the risk of major bleeding, so patients and their doctors are going to have to be willing to accept this higher risk.”

Because each of these three newer blood-thinning agents is being developed in a fixed-dose pill with more predictable pharmacokinetics, there’s no need for titration and less need for ongoing monitoring of patient response. As a result, these newer oral agents are expected to steal market share from Coumadin in chronic care and the heparins in acute care, and to expand the number and types of patients who will benefit from their use (e.g., beyond the treatment of acute thrombotic conditions during hospital stays), to include the chronic, long-term treatment following a heart attack, and to be used preventively, to reduce the risk of stroke and other thrombotic events for certain high-risk patients), says Decision Resources analysts.

“In the U.S., we tend to prefer drugs in pill form over injection, and this does put some drugs at a disadvantage because oftentimes pills are chosen over injections even if they are less effective or less well-tolerated,” says Lasky of IMS Consulting.

The convenience of prescribing anti-coagulants and anti-platelet drugs in pill form also provides an important advantage for many prescribers. “Today, there are simply not enough cardiology specialists out there to cope with the growing number of CV patients, so more and more, patients are receiving CV treatments from their primary care physicians,” says Lasky. “Fixed-dose pills are just easier to titrate and dose and manage in the primary care market, and this provides a real advantage by filling an unmet need.”

Market prognosis
“Today, there’s one overarching theme in traditional CV markets,” says Lasky of IMS Consulting. “Everyone’s preparing for ‘life after’ — Life after Lipitor…life after Diovan…life after Plavix.” And for brand managers at these aging-yet-lucrative franchises, there’s still no consensus over whether the best approach is to redouble DTC and detailing efforts, or to essentially abandon ship.

“Especially in this era of payor-decision-based prescribing practices — which often favor using the generics first — the ability to allow doctors to spend more money on advanced, targeted treatment using branded drugs often requires extra effort,” says Lasky. “Particularly when considered for use with high-risk or fragile patients, the safety profile (better or worse) of any drugs will come into sharper focus against whatever else is out there.”

“In many ways, a statin’s a statin’s a statin, especially for the garden-variety patient. For this patient population, it’s often harder for branded drugs to fend off the inevitable generic intrusion,” says Bolling of Roska Healthcare. “Unless there’s clinical data to back up claims of superiority, it doesn’t make a whole lot of sense for a branded statin to spend a lot of DTC money trying to convince people that their product is better than generic simvastatin, because other factors, such as pressure from the insurer or PBM, so often trump the prescribing decision.”

However, others note that strategies are available for those drug companies that are still willing to put up the good fight to protect the beach head once the generic insurgents have broken through.

For instance, some suggest that brand franchises must negotiate aggressively with distributors, managed-care companies and other insurers to maintain the most advantageous formulary tier position for their drugs, and work with managed-care partners to offer rebates, vouchers and cost savings through bundling. “Considering how pervasive and restrictive formulary constraints tend to be today, pharma companies must keep positioning their medications to gain the highest possible tier designation,” says Vogenberg.

RICHARD CAMPBELL, REGAN CAMPBELL WARD/MCCANN

Most agree that proactive detailing also remains a key outreach effort. “If there’s still a solid story to be told about how, for instance, your branded drug’s greater efficacy, better tolerability, reduced side effects, better consistency of manufacturing, advantageous dosing or administration strategy can improve patient outcomes and increase compliance (for example, by improving convenience and reducing side effects), you need to make that case loud and clear,” says Richard Campbell, strategic partner, Regan Campbell Ward • McCann (New York).

Another approach—but one with limited utility—is to try to compete with better pricing, says Campbell, although he admits this is “rarely a winning strategy” because generics are sold at such a steep discount from branded prices. But if manufacturers “can get a little closer to the generics on price using vouchers and rebates, they may be able to help patients and providers justify the ongoing use of the branded medication.”


In it for the long haul
High blood pressure and high cholesterol share another distinction that adds to the compliance challenge. “Both are pervasive and easily diagnosed so it’s completely conceivable for a patient to get a diagnosis of one or the other at 40 or even younger, and potentially face 30 or 40 years of ongoing treatment,” says Earl of Decision Resources. These patients will have to remain vigilant about taking various drug therapies — medications that will certainly provide clinical benefits, but these are often benefits that the patient will neither see nor feel directly.

 

And if many of the drug companies had their druthers, some of those prescriptions would come even earlier in the patient’s life, across a broader spectrum of lower-risk patients. The question of when to start a patient on therapy is another prickly one in the pharma community.

Today, Pfizer’s anti-cholesterol drug Lipitor (atorvastatin) is not only the best-selling drug in the CV sector, but it was the best-selling medicine in the world last year, as well. In 2007 alone, Lipitor sales brought in $12.8 billion in revenue worldwide for Pfizer, accounting for more than a quarter of the company’s total revenue, according to its 2007 Annual Report.

The eventual loss of its market exclusivity in 2011 will be a painful one for Pfizer, if Merck’s experience with Zocor (simvastatin) is a guide. After enjoying peak U.S. sales of $5.6 billion in 2002, the immediate entry of multiple generic versions of simvastatin in 2006 contributed to Zocor’s 2007 sales falling to $876 million.

And since the introduction of generic simvastatin, sales of Lipitor have already been affected. For example, according to IMS Health, Lipitor’s U.S. sales of $8.1 billion in 2007 — healthy by any standards — were already down by 8.3% from its 2006 peak of $8.7 billion. And worldwide, 2007 sales were down by 1.6% from the year before, in part due to the availability of generic simvastatin.

Last June 18, Pfizer settled a lawsuit with generics manufacturer Ranbaxy Laboratories (which has been trying to launch generic atorvastatin in key markets), allowing the Indian company to launch its generic version of Lipitor on November 30, 2011. This effectively extends the Lipitor monopoly beyond March 2010, when its basic patent expires was originally set to expire.

Lipitor’s rapidly approaching patent expiry is not the only thing weighing on Pfizer’s CV marketing teams. In late 2006, the development of the company’s next-generation cholesterol drug torcetrapib — which had already been hailed as the next likely heir to the Lipitor throne, thanks to its anticipated ability to not only lower LDL or “bad” cholesterol but to raise HDL or “good” cholesterol, as well — was suspended during Phase 3 clinical trials, due to an increase number of deaths among the patients taking it. In light of these setbacks, Pfizer announced this past September that it plans to shift its R&D focus away from CV drugs, in order to put greater focus on cancer, Alzheimer’s disease and biotechnology drugs, which it expects will be more profitable.

“Pfizer’s pullout of the CV arena to focus its R&D efforts elsewhere highlights the highly competitive nature and maturity of this market,” says Green of Decision Resources.
Similarly, last April 28, FDA rejected Merck’s experimental cholesterol drug, which it had planned to call Cordaptive. Like Pfizer’s torcetrapip, it was also aiming to slay one of cholesterol’s main dragons by raising HDL levels while lowering LDL cholesterol.

The failure of Cordaptive wasn’t Merck’s only recent setback in the CV sector. Merck’s combination pill Vytorin (co-marketed with Schering Plough) — which combines Merck’s statin Zocor with Zetia (ezetimibe), another drug in Merck’s portfolio, that blocks the absorption of cholesterol absorption from the gut — still enjoys patent protection, allowing both companies to charge branded prices for it.

However, Vytorin suffered its own black eye recently when Merck and Schering-Plough announced the results of a study that showed that Vytorin may not be any more effective than using Zocor (or its generic equivalent) alone. The companies were roundly criticized because that clinical trial (the so-called ENHANCE trial) was completed in April 2006 but its lackluster findings were not published until January 2008 — and during the interim, the two companies continued to advertise Vytorin as a better alternative to Zocor. As a result, both companies are currently defendants in a growing number of civil class-action lawsuits related to Vytorin’s potentially misleading advertising, and are currently being investigated by the U.S. Justice Dept. to determine whether the companies deliberately delayed releasing the ENHANCE results in order to maintain sales of Vytorin and Zetia.

Despite these setbacks and in response to Pfizer’s announcement that it was pulling out of the CV arena, Merck reiterated its commitment last November to ongoing research into heart disease, cholesterol and hypertension drugs. CV-related drugs contributed nearly a third (29%) of Merck’s total 2007 revenue, according to industry reports.

Pushing for earlier, even off-label use of statins
Just how far is society willing to go when it comes to pharmaceutical intervention for the purpose of reducing the risk of heart attack, heart failure and stroke? AstraZeneca took its lumps recently, when it set out to demonstrate the clinical benefits of earlier statin use in low-risk patients. The resulting JUPITER study (for Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin [AstraZeneca’s Crestor]) turned out to be one of 2008’s most controversial clinical trials.

In that trial, whose results were published November 9 in the New England Journal of Medicine (NEJM, Vol. 359:2195-2207), 17,802 “apparently health men and women” with normal cholesterol levels but elevated levels of C-Reactive Protein (CRP; thought to be a biomarker for artery inflammation, were given the statin Crestor or a placebo. The trial set out to determine if prolonged use of a statin would reduce the incidence of heart attacks, strokes and sudden death from cardiovascular disease, and aimed to “address the question of whether apparently healthy persons with levels of LDL cholesterol below current treatment thresholds but with elevated levels of high-sensitivity C-reactive protein might benefit from statin therapy.”

The study seemed to show that in otherwise healthy persons without high cholesterol but with elevated levels of CRP, taking rosuvastatin “significantly reduced the incidence of major cardiovascular events.” In fact, after the results were announced, doctors at the AHA predicted that the JUPITER study might lead to as many as 7 million more Americans to consider taking cholesterol-lowering statin drugs such as Crestor, Lipitor, Zocor and others.

But critics quickly slammed everything from the way the study was carried out, to the fact that Crestor maker AstraZeneca funded it itself. Another potential conflict was focused on the fact that the lead investigator, Paul Ridker of Brigham and Women’s Hospital in Boston, owns a patent on the $20 test that is used to measure a patient’s CRP levels.
“Drug companies invest hundreds of millions of dollars into scientific studies to test the efficacy and safety of a particular drug for a particular indication, in order to help the entire healthcare community to better understand what’s going on,” says Lasky of IMS Health. “AstraZeneca wouldn’t be doing its job if it didn’t do its study and share the results as early as possible — and these results were not released to an empty room — they were released to a packed house because so many throughout the healthcare community wanted to know what the study showed.” He adds: “Now that AstraZeneca has made its case regarding the potential benefit of even-earlier statin use, others (payors, PBMs, managed-care groups) need to state their case and let the debate move forward.”

In an editorial published in the same issue of NEJM that published the JUPITER results, Stanford cardiologist Dr. Mark A. Hlatky wrote that while the relative risk reductions in the study “were clearly significant,” the “absolute” differences [i.e., the actual number of patients with better outcomes] were “more clinically important.” Out of the 8,901 test subjects, the proportion with “hard cardiac events” was reduced from 1.8% to 0.9%. In effect, the difference between the test group and the control group amounted to reducing 1.8 events to one event. the absolute benefits of treatment must be large enough to justify the associated risks and costs.”

When it comes to justifying additional payments for drug therapies as a pre-emptive step for low-risk patients different stakeholders have different metrics by which to project potential ROI. For instance, Vogenberg of EPS and IIH notes that for diabetes, employers and payors can often see an ROI of six months to a year, in terms of the immediate health turnaround that is possible when a diabetic is able to maintain glycemic control. “With CV problems, much longer time horizons are often required for the payor or employer to see the actual impact of more proactive outreach, in terms of reduced hospitalization, reduced risk of heart attack or stroke, disability or premature death that results from prolonged high blood pressure or high cholesterol.”

For many managed care providers, this provides a conundrum. “If payors end up paying now for earlier drug use in order to cut the risk of stroke by, say, 50% over the next 20 years, they are not likely to benefit from that risk reduction in the end, because patients tend to move through different managed-care providers every few years,” says Campbell of RCW. “Where the risk and reward end up really becomes something of a hot potato — which insurer is going to end up with the patient when a CV event actually happens or doesn’t happen?”

 

JAMES NOTARO, CLINICAL SUPPORT SERVICES

“The evidence indicates that using statins as preventive therapy in primary prevention reduces morbidity and mortality rates but the question is, ‘At what cost?’” says James Notaro, RPh, PhD, principal, Clinical Support Services, Inc. (Buffalo, NY), a medication therapy management company that helps its clients (HMOs, Medicare Part D prescription drug plans and other groups responsible for prescription benefit programs) to build clinical profiles of patients who are using certain drug therapies in order to identify utilization that is not evidence-based or cost-effective and make recommendations for alternative treatment agents. “The cost-effectiveness literature suggests that statin use in primary prevention at branded statin costs, would be in the $200,000-$300,000 per quality-adjusted life year range. For the U.S. it’s difficult to justify preventive therapy at that price point,” he adds.

However, Notaro notes that the availability of generic statins — which provides a less expensive option for long-term use — may help all stakeholders to justify the earlier, more-widespread use of statins for the prevention of cholesterol-related problems among lower-risk patients. “The use of generic statins brings the cost closer to or below the $45,000 per quality adjusted life year, which is generally considered acceptable,” he says. PC