Can a “calculator” really tell doctors who should be on Lipitor?

November 13, 2013- By Steven E. Greer, MD

The AHA released the long-awaited new guidelines that recommend which patients should be on a cholesterol-lowering statin, such as Lipitor or Crestor. The panel of experts incorporated evidence-based medicine into the guidelines, perhaps better than any other medical society guideline panel has done previously. However, the panel also used some very dubious statistical tools as well.

According to Read more »

Overview of rHGH therapy

January 14, 2015- Interviewed by Steven E. Greer, MD

We interviewed Dr. Shlomo Melmed, Director of the Clinical Research Institute and Dean of Faculty at Read more »

Exclusive: Why did Dr. Nissen resort to secret tapes?

February 23, 2010- By Steven E. Greer, MD

Many in the cardiology community are a bit confused as to why Dr. Steven Nissen Read more »

CBS allows TV doctor to make egregious claims about statins

Can a “calculator” really tell doctors who should be on Lipitor?

Nortin Hadler, MD: lack of evidence for widespread statin use

The risk of diabetes associated with statin drugs

“You’re telling me this now?” Why the news is suddenly critical of statins and antidepressants

 Sanjay Kaul, MD: The Crestor JUPITER indication label expansion

Exclusive: President Bush had controversial coronary CT-scan as routine screening leading to questionable stent

August 7, 2013- By Steven E. Greer, MD

The press has reported extensively about President George W. Bush (The 43rd President) receiving a controversial coronary stent after a routine annual exam found a blockage in an unspecified coronary artery. A spokesperson for Mr. Bush said that the president received his exam from the Dallas Cooper Clinic, and was having no symptoms. After the stent was placed, the president was in good spirits.

The Healthcare Channel has learned that the Cooper Clinic administers coronary CT-scans as routine screening measures during the “Executive” physical exams, and that no other symptom or test is needed to trigger a CT-scan. Even if the president were having chest pain, or a stress test had revealed ECG changes, then a coronary CT-scan is not the best study to order.

Reports in the news from unknown sources claim that the president failed a stress test during his exam, and that those ECG changes triggered the CT-scan. Our information conflicts with those reports in that CT-scans are performed as routine screening for all “Executive” exam patients.

In addition, the stress test rumored to have taken place is not an Read more »

Is the healthcare industry a bubble slowly deflating?

December 3, 2011

Steven Greer, MD- The Healthcare Channel

Two weeks ago, we issued the story, below, about possible layoffs and cuts in the healthcare industry due to a “Healthcare Bubble”. At the medical center level, we said that it would be likely that doctors, normally a profession with great job security and in demand, would see layoffs. To add a real case example to that story, Cedars Sinai in Los Angeles, a medical center with a profit margin far greater than the national average and often the treatment choice for celebrities, is now completely closing its psychiatry department to save money. Their pediatric and OB/GYN services have also been scaled back.

Now, CMS Medicare is planning to make it much more difficult for medical centers to perform the most lucrative of procedures (i.e. spine fusion, joint replacement, and numerous cardiac procedures like stents and ICDs). Just a few years ago, many medical centers greatly expanded their cardiac cath labs to try to perform more coronary stenting. Clinical data and evidence of unnecessary implantation of stents has already decreased the volume of stenting. These new CMS measures might lead to another 20% reduction, according to a cardiologist we spoke with. Spine fusion cases are also very vulnerable to reductions in case volumes due to fears of Medicare audits finding the cases to have been unnecessary.

Already, the bad economy, high unemployment, and fewer insured, have caused reductions in procedure volume. CMS seems to be adding to the strangling pressures. We expect to see significant layoffs in the ranks of spine surgeons, orthopedic surgeons, and interventional cardiologists, if these case volumes are reduced.

Related to stocks, we continue to believe that Medtronic would do well to spin off the spine and ICD divisions. Questions about strategic divestitures were common from callers on the recent earnings call. Edwards Lifesciences (EW) will also face a much more challenging reimbursement climate making for a slower launch of their new TAVR Sapien valve, in our estimation.

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Is the healthcare industry a bubble slowly deflating?

November 15, 2011

By Steven Greer, MD

Throughout the economic depression that began in 2007, the healthcare industry has continued to add jobs. Healthcare providers are still in demand and command good wages and job security. However, can the good times last much longer as the global depression seems to be worsening rather than improving?

The “Super committee” in congress might trigger cuts next week to the HHS Medicare/Medicaid budget and the White House is also advocating cuts. The passage of the ACA health insurance reform law also requires $500 Billion in cuts. Governments have poor track records at making cuts to entitlements, but the private sector might be the most powerful force to enact cuts to the healthcare industry.

With the high unemployment rates has come a lower percentage of the population with full health insurance. This has already had a powerful impact on the healthcare industry. Fewer visits to the doctor and fewer elective (or even not so elective) procedures, combined with a higher mix of low-reimbursing Medicaid, is driving cost consciousness amongst the consumer patients and the hospitals.

We previously reported how newly-approved expensive branded drugs are selling poorly. Once deemed a positive event for a company, an FDA drug approval is now associated with significant reductions in share prices for the companies as investors become disappointed and change their expectations. $100,000 cancer drug prices might represent a pharmaceutical bubble.

JP Morgan’s medical device analyst issued a report detailing many of these repressive influences on the medical device sector. For the large companies such as Johnson and Johnson, Abbott, or Medtronic, the earnings growth rates have decreased from 10% down to 3%, and that is after considerable cost cutting measures were implemented in the form of mergers and layoffs.

Cutting operating expenses is a temporary measure and no substitute for revenue growth. When the companies have trimmed back to the bone, will growth turn negative?

If the ACA law continues to be implemented and is not overturned by the Supreme Court or the new congress next year, it will add millions of patients to the Medicaid system, further stressing state and medical center budgets, will we see salary cuts to doctors and layoffs in the healthcare sector?

If Greece, Italy, Spain, Ireland, etc. send Europe into a double dip depression, what will be the impact to the healthcare industry?

We will be interviewing healthcare economists, policymakers, and hospital executives over the next few months to try to answer some of these questions.

 

Greg Fontana, MD: Transcatheter aortic valves

Greg Fontana, MD, Co-Chair of surgery at Cedars Sinai Medical Center, discusses the Edwards Sapien transcatheter aortic valve for which he is the PI of the US trials called PARTNER. Dr. Fontana explains the design of the valve and differences between the Medtronic Corevalve.

A primer on JNJ’s Xarelto for A-fib

Update: November 15, 2010

The following is from a Barclays Capital research note (Mark Purcell et al)

BAYER/JNJ: Why Xarelto doesn’t seem superior

ROCKET-AF, the pivotal trial for Xarelto in stroke prevention, has demonstrated that the drug was non-inferior to Warfarin with regard to all-cause stroke and non-central nervous system embolism. Disappointingly, however, the intention-to-treat superiority analysis failed to show the drug had an advantage, statistically, over Warfarin. This would suggest that the drug failed its pre-specified test for superiority. The ROCKET-AF design paper published in the American Heart Journal states: ‘If the noninferiority criterion is satisfied, then superiority for the primary efficacy end point will be tested in the safety population…’. The safety population is NOT the per protocol population used to show the 21% risk reduction mentioned in the press release and hence the trial seems to have failed the test. This means that the commercial perspectives are unclear relative to the competitor Pradaxa, as differentiation will have to rely on dosing and other aspects that may be considered secondary to the primary efficacy and bleeding risk.

(The following is our original note)

November 9, 2010

One of the bigger drug trials to be discussed next week at the AHA meeting will be the Bayer/JNJ trial called ROCKET-AF, which studied Xarelto (rivaroxaban) (a direct factor Xa inhibitor) to prevent stroke in patients with non-valvular atrial fibrillation. Recall, Xarelto already went before an FDA advisory committee to review the indication to prevent deep vein thrombosis (DVT) after orthopedic surgery and the FDA surprisingly issued CR letter, effectively rejecting that indication. The FDA wanted more data on possible liver damage caused by the drug.

Bayer/JNJ did not bother to reply to the CR letter for DVT and they now plan to pursue the bigger indication of A-Fib. Therefore, ROCKET-AF is crucial to the future of this drug.

The unmet clinical need that Xarelto would satisfy is an oral anticoagulant that is easier to take and safer than warfarin. Boehringer Ingelheim recently received FDA approval for their own warfarin alternative called Pradaxa (dabigatran) (a direct thrombin inhibitor downstream in the cascade from factor Xa, see our previous video stories). Although Pradaxa’s RE-LY trial was a non-inferiority trial, the drug was actually superior to warfarin. The big question to be answered at the AHA is whether Xarelto too was superior. The press release did not address this.

In addition to the superiority claim, which is not in the Pradaxa label, by the way, the marketing battle between Xarelto and Pradaxa will also revolve around the QD dosing for Xarelto versus the BID for Pradaxa. Also, the dual renal/liver excretion of Xarelto makes it safer for renal failure patients, whereas Pradaxa is excreted only by the kidneys and the dosage must be reduced.

Harlan M. Krumholz, MD, of Yale wrote, “Now we await the ROCKET AF presentation. The key questions will be:

• Were the event rates comparable to what might be expected in practice — or is there evidence that the study population was highly selected?
• Was the warfarin treatment optimized? How well was the INR maintained?
• Are there any safety concerns with rivaroxaban? How do bleeding rates compare?
• Is there any suggestion that the drug is particularly good or bad for a particular subgroup? This would be an exploratory analysis and would not likely be considered definitive.
• Is there any evidence that rivaroxaban is more effective than warfarin?

And then, if at the end of the day, rivaroxaban really looks to be no better than warfarin — will it find a niche in clinical care?”

Sanjay Kaul, MD, of Cedars Sinai Medical Center, and member of the first Xarelto FDA AdCom, wrote, “Rivaroxaban represents the first of an interesting class of drugs (oral Xa inhibitors) that have the potential to alter the landscape of anticoagulant therapy. Whether rivaroxaban finds a niche in clinical care will depend on the balance of ancillary advantages in convenience, safety, and tolerability versus ‘noninferior’ or ‘superior’ efficacy. if superiority is demonstrated, then it will likely be eminently competitive with the recently approved dabigatran.”

Sanjay Kaul, MD: The Crestor JUPITER indication label expansion

Dr. Kaul comments on Crestor

February 10, 2010

The HCC received comments from Dr. Sanjay Kaul about the recent label expansion for AstraZeneca’s Crestor drug. Dr. Kaul was a voting member of the FDA advisory panel for this indication.

Dr. Kaul: Here are my comments for whatever they are worth. There are 2 elements of the FDA’s approval of rosuvastatin that are noteworthy.

First, the label is appropriately conservative in that only a claim for reducing the risk of stroke, MI and revascularization procedures is allowed. Two other component events (hospitalization for unstable angina and death from cardiovascular causes) of the primary quintuple composite endpoint were not allowed in the claim because rosuvastatin failed to impact these outcomes. The reduction in total mortality with rosuvastatin was driven by reduced risk from non-cardiovascular causes of death, principally cancer-related mortality, which is likely to be a spurious observation.

(Editorial note: See The HCC interview with Dr. Guyatt who first said this last year; that the cardiac deaths were not reduced in he JUPITER trial)

Second, the new label includes one additional cardiovascular risk factor such as hypertension, low HDL-C, smoking, or a family history of premature coronary heart disease in addition to the age and elevated hsCRP required for patients to be enrolled in the pivotal JUPITER trial. In JUPITER the treatment benefit was observed only in the group of patients that had at least one additional risk factor (nearly 50% of the individuals enrolled). Patients with age and elevated hsCRP alone (nearly 25% of the patients) failed to exhibit a significant treatment benefit.

The implication of this specific language in the label is that the FDA did not endorse hsCRP for either risk stratification or for therapeutic triage. The NCEP ATP III guidelines already offer statins as an optional treatment for primary prevention in individuals with at least 2 risk factors and LDL levels in the range of 100-129mg/dl.

In my opinion, the label is firmly anchored in evidence and appropriately conservative.

Sanjay Kaul, MD

Professor, Cardiologist

Cedars Sinai Medical Center

Sanjay Kaul, MD: Discusses the NY Times article on Crestor risks

March 31, 2010

The NY Times featured a front-page article on March 31 discussing the risks of expanding the indication for the statin Crestor to people with normal levels of cholesterol. This story came on the heels of another story appearing in Time magazine that questioned statin risks and benefits in women. We asked cardiologist Sanjay Kaul for his thoughts.

Dr. Kaul: Although statins have been shown to increase the risk of incident diabetes, the key question to ask is whether their favorable impact on cardiovascular outcomes are reduced in those that are rendered diabetic by statin therapy. It is a paradox that interventions that increase incident diabetes (such as thiazide diuretics, beta blocker, statins, even niacin) improve cardiovascular outcomes. In contrast, none of the interventions (with the possible exception of metformin) that reduce incident diabetes or improve glycemic control (such as TZDs, nateglinide, insulin, sulfonylureas,

GLP-1 analogs, etc.) have been shown to reduce cardiovascular outcomes.

I think the broader message of the NY Times article is on target.

Lifestyle modification trumps pharmacologic intervention for primary prevention.

With regards to the Times magazine story, a treatment benefit of statin, be it total cardiovascular disease or total mortality events, that is not statistically discernible from null in nearly 20,000 subjects, does not provide robust evidence of benefit in favor of statins in women. The total cardiovascular disease benefit observed with statins in the exclusively primary prevention trials is driven by the results of JUPITER, which is likely to be an overestimate given the premature stoppage of the trial. Furthermore, the 5-year numbers needed to treat (NNT) estimates in JUPITER are unlikely to be reliable. The trial was stopped at 1.8 years. So, how can one simply extrapolate the NNT to 5 years and assume that the benefits observed at 1.8 years are going to persist at 5 years? People who insist on extrapolating NNT to time frames beyond the actual period of follow-up should be reminded of the perils of random variation, especially when the trials are stopped prematurely.

Many experts have disputed the facts reported in the Times magazine story and have expressed concerns that the story will end up discouraging women to control their risk factors. I did not see anything in that report that is not factual or that encourages women to quit controlling their risk factors. Instead of criticizing the article, we should acknowledge the holes in the evidence that the Times report rightly identifies and generate data to shore up the evidence.