Tuesday, November 15, 2016

What to Believe and Do About Statin-Associated Adverse Effects

The Statin craze is a long way from dead yet but the medical establishment is gradually coming to terms with the bad side-effects of statin use. At one time they denied any bad side-effects.  So the article excerpted below is interesting.  It is particularly interesting for the two sentences I have highlighted below.  Basically, medical researchers and drug companies just didn't want to know about side-effects from their new wonder drug.

And they still don't.  The summary below does not capture well, for instance, the mental effects of statins.  These are widely reported by patients but are virtually dismissed below.  Statins can give you Alzheimer-type symptoms so it is possible that the upsurge in Alzheimers in recent years is in fact misidentified statin use.

So the report below does serve as a warning but should be regarded as a minimal warning.  The problems are undoubtedly greater than the author, Paul D. Thompson, acknowledges.  Thompson is of course convinced that the benefits of Statins outweigh the problems but on my reading of the literature, that only applies to people who already have experienced heart problems: angina, stroke, heart attacks.  Dosing up people with statins as a general preventive measure seems on my reading to be devoid of ANY benefit and likely to do harm.  As another curent article in JAMA says: Statins for Primary Prevention; The Debate Is Intense, but the Data Are Weak

Possible statin-associated adverse effects include diabetes mellitus, hemorrhagic stroke, decreased cognition, tendon rupture, interstitial lung disease, as well as muscle-related symptoms.1 Statins increase the risk of diabetes consistent with the observation that low cholesterol levels increase diabetes risk.1 Although statins reduce total stroke, they increase the risk of hemorrhagic stroke consistent with the observation that low cholesterol levels are associated with an increase in hemorrhagic stroke.1 Statins appear to reduce or have no effect on cognitive decline.1 Tendinopathies and interstitial lung disease have possible mechanistic links to statins, but their association with statins is based solely on a small case series.1 The frequency of these possible drug-related complications is unknown but is low and outweighed by the vascular benefits of statins therapy.

Statin-associated muscle symptoms are the most frequent statin-related symptoms. Experts agree that statins can cause muscle symptoms with marked increases in creatine kinase (CK) levels, usually defined as 10 times the upper limits of normal because this has been observed in randomized clinical trials (RCTs) with an estimated occurrence of 1 additional case per 10 000 individuals treated each year.2 In addition, statins can cause a necrotizing myopathy with antibodies against hydroxyl-methyl-glutaryl Co-A reductase.1 This condition must be recognized promptly because it can lead to persistent myopathy. These patients present with muscle pain and weakness plus marked increases in CK levels that do not resolve with drug cessation. Statin-associated necrotizing myopathy is newly recognized and rare but may be more frequently diagnosed now that a commercial test for the antibody is available.

In contrast, there is considerable debate as to whether statins can produce milder symptoms such as myalgia, muscle cramps, or weakness with little or no increase in CK levels. Collins et al2 reviewed the possible adverse effects found in RCTs of statin therapy and concluded that statin-associated muscle symptoms without marked CK elevations do not exist or are extremely rare because they are not reported in the statin RCTs. These authors suggested that these symptoms may be inappropriately attributed to statins due in part to patients being warned of such possible adverse effects by their clinicians.

Most clinicians, however, are convinced that these symptoms exist and are caused by statins. The incidence of statin myalgia has been estimated at 10% from observational studies.1 The Effect of Statins on Skeletal Muscle Performance (STOMP) study is the only randomized, controlled double-blind study designed specifically to examine the effects of statins on skeletal muscle.3 The STOMP trial had predefined criteria for statin myalgia, which included onset of symptoms during treatment, persistence for 2 weeks, symptom resolution within 2 weeks of treatment cessation, and symptom reappearance within 4 week of restarting treatment. Nineteen of 203 patients treated with statins and 10 of 217 patients treated with placebo met the study definition of myalgia (9.4% vs 4.6%, P = .054). This finding did not reach statistical significance, but it indicates a 94.6% probability that statins were responsible for the symptoms. This result occurred even though the study participants were young (mean age, 44.1 years), healthy, and treated with statins for only 6 months. Creatine kinase values were not different between the 2 groups. These results not only suggest that the true incidence of statin myalgia is approximately 5% but also support the observation that approximately 10% of patients will report symptoms of myalgia. Collins et al2 reanalyzed the STOMP trial data after including 29 patients treated with atorvastatin and 10 with placebo who discontinued participation because of personal reasons, yielding a P value of .08 and used this finding to support their assertion that statins do not cause muscle symptoms without markedly increased CK levels.

Diagnosing true statin-associated muscle symptoms is difficult. In the Goal Achievement After Utilizing an Anti PCSK9 Antibody in Statin Intolerant Subjects (GAUSS-3) study,4 the presence of statin myalgia was determined by randomly assigning patients with presumed statin muscle symptoms to receive either 20 mg of atorvastatin or placebo each day for 10 weeks followed by a 2-week hiatus before crossover to the alternative treatment. Only 209 patients (42.6%) developed muscle symptoms during atorvastatin treatment. An additional 130 (26.5%) developed muscle symptoms during placebo-only treatment, 48 (9.6%) developed muscle symptoms during both treatments, and 85 (17.3%) did not develop symptoms during either treatment.

Other evidence supports the idea that statins can cause skeletal muscle symptoms without abnormal CK values. Muscle biopsies show differences in gene expression among patients with statin-associated muscle symptoms during statin treatment and compared them with asymptomatic controls.5 Statins also produce slight increases in average CK levels and augment the increase in CK observed after exercise.1 Rhabdomyolysis is more frequent in participants in RCTs who are receiving statins and have variants in the gene for solute carrier organic anion transporter family member 1B1 (SLCO1B1),2 which regulates hepatic statin uptake. The SLCO1B1 gene variants that reduce hepatic uptake allow more statin to escape the liver and enter the extra portal circulation and ultimately skeletal muscle. The SLCO1B1 variants are also associated with mild muscle adverse effects in study participants treated with statins.6

How could the statin RCTs miss detecting mild statin-related muscle adverse effects such as myalgia? By not asking. A review of 44 statin RCTs reveals that only 1 directly asked about muscle-related adverse effects.7 In the STOMP trial, investigators called patients twice monthly to ask specifically about muscle symptoms.

JAMA. 2016;316(19):1969-1970. doi:10.1001/jama.2016.16557


Trump Plans Ambitious Agenda

Donald Trump has announced an ambitious agenda for his first 100 days in office, but it's becoming increasingly clear that achieving it will be more difficult than he suggested during the campaign.

At the top of his list, which he outlined during the past several months, is repealing President Barack Obama's signature health care law, known as Obamacare. Trump has said the program is costing consumers too much, is damaging the economy and represents an unwise intrusion of the government into the health care system.

Prospects are good that the law could be repealed within several weeks of Trump's inauguration as president because voters this week placed the White House and Congress under GOP control. Political scientist Ross Baker of Rutgers University says repealing Obamacare is one of the issues on which Trump can find common ground with congressional Republicans from day one. And Senate Majority Leader Mitch McConnell said Wednesday that repeal is a top priority for the Senate GOP. The House is likely to agree.

There are several sticking points, however, such as what to do about the estimated 24 million Americans who would lose health insurance if Obamacare were abolished. How Trump and fellow Republicans solve this problem remains unclear.

Another area of apparent agreement within the GOP is immigration, one of Trump's biggest talking points during the campaign. The billionaire real-estate developer has big plans, and congressional Republicans seem willing to move forward with the required legislation despite expected Democratic opposition.

Trump wants to build a wall between the United States and Mexico, and have Mexico pay the bill. Trump also wants to deport millions of immigrants who entered the United States illegally and have committed crimes since they arrived here. One problem, and it's a vexing one for Trump, is that the government of Mexico says it won't pay for the wall. And specifics are still lacking on the deportation plan.

Trump has talked about temporarily prohibiting the entry of Muslims into the United States because some of them might be terrorists. This Muslim ban, if Trump proceeds with it, is likely to be challenged in court, tying up the plan for many months until it is resolved by the judiciary.

Trump wants to persuade Congress to cut taxes and reform the tax system, but this would also take many months and it's uncertain if Democrats and Republicans are willing to take it on.

Trump wants to reduce federal regulation, and he can do much of this through executive action, bypassing Congress. This is likely to include pulling back a number of Obama's controversial executive actions and reversing or modifying the Environmental Protection Agency's plans to make it much harder to build and operate coal-fired power plants. This was an effort to limit climate change, but Trump has questioned the validity of human-caused global warming.

Trump wants to void trade deals made by Obama, such as renegotiating or withdrawing from the North American Free Trade Agreement. And this appears to be very possible.

Other items on Trump's to-do list will be tougher to implement. Trump favors imposing term limits on Congress but McConnell opposes them. And McConnell is less than enthused about Trump's plan to boost spending on infrastructure, apparently because it would cost so much money.

Another big decision will be naming a Supreme Court nominee to replace the late Justice Antonin Scalia. Trump aides say he will quickly make his choice, possibly on his first day in office. This will set up a major confrontation in the Senate as Democrats are expected to rally against Trump's choice.



Disenfranchisement, Democrat Style

In an interview with actress Gina Rodriguez, Barack Obama was asked the following question: “Many of the Millennials, Dreamers, undocumented citizens — and I call them citizens because they contribute to this country — are fearful of voting. So if I vote, will immigration [officials] know where I live? Will they come for my family and deport us?”

Obama replied, “Not true. And the reason is, first of all, when you vote, you are a citizen yourself and there is not a situation where the voting rolls somehow are transferred over and people start investigating, etc. The sanctity of the vote is strictly confidential in terms of who you voted for. If you have a family member who maybe is undocumented, then you have an even greater reason to vote.”

Did Obama just declare that it was ok for illegal immigrants to vote? It seems so, though it’s not case closed because he went on to say illegals are “counting on you to make sure that you have the courage to make your voice heard.” His deliberately ambiguous words are alarming given all that Obama has done to eviscerate Rule of Law on the immigration front.

Meanwhile in Virginia, it was recently learned that Democrat Gov. Terry McAuliffe has successfully granted 60,000 ex-convicts voting rights in time for voting in the election, helping tip the state in favor of his long-time friend Hillary Clinton. It had been initially reported by his office that he was able to review and sign only 13,000 approvals after the state courts overruled his attempted illegal blanket pardon of more than 200,000 ex-convicts. In fact, those pardoned felons received voter registration forms with a letter from McAuliffe with pre-paid return postage.

It’s clear that Democrats have little problem with the legality of voters, so long as those voters support their candidates. What’s ironic is just how much Democrats wail about voter disenfranchisement, all while disenfranchising citizens with their continued efforts to get votes from illegal immigrants and felons. Is it any wonder that many Americans believed Donald Trump when he talked about the election being rigged?



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1 comment:

C. S. P. Schofield said...

"There are several sticking points, however, such as what to do about the estimated 24 million Americans who would lose health insurance if Obamacare were abolished. How Trump and fellow Republicans solve this problem remains unclear."

Since the Media and the Democrats are going to claim that tens, if not hundreds, of thousands of people will lose coverage with the repeal of Obamacare, Trump and the Republicans should do nothing at all to 'mitigate' this. If nothing you do will change anything for the better, don't do anything. The market, if allowed to, will ultimately find its own level.