Hypertension and cholesterol drugs, side effects

ACCORD study - Diabetes two drugs - Other drugs - Conclusion

In addition to diabetes 2 medications, ACCORD study participants were given both, hypertension and cholesterol drugs. Those in the intense arm of the study were receiving significantly higher than standard doses - as much as needed to push blood pressure and cholesterol levels down to their normal range. Little is known about possible adverse health effects of such treatment, especially for patients with diabetes and high risk of cardiovascular complications.

That didn't prevent study's creators to try to bring study participants' blood pressure and cholesterol numbers "under control" with intense drug treatments.

Let's take a look of hypertension drugs and some of their known side effects in standard doses. The main four groups are diuretics, beta-blockers, calcium channel blockers and ACE inhibitors. The study doesn't specify which hypertension drugs were used, nor in what frequency or dosages, so we can only talk in general terms.

It is generally suspected that hypertension drugs may contribute to the development of diabetes. Although recent studies indicate that it may be limited to diuretics and beta-blockers, it is far from certain, especially for unusually higher than standard doses. At present,

there is no reliable basis to pre-determine whether a hypertension drug will contribute to one's individual diabetes, or not.

Diuretics reduce blood pressure by stimulating fluid excretion. By that, they also precipitate loss of minerals, including magnesium, which in turn puts you at increased risk of heart attack, including sudden cardiac death.

So called calcium channel blockers (CCB), which work by reducing cellular intake of calcium (needed for muscle contraction, contributing to blood pressure) are shown to increase the risk of heart attack by 27% and 60%, for long-acting and fast-acting CCBs, respectively (European Cardiology Society report and University of Washington, Seattle).

Another class of hypertension drugs, so called ACE inhibitors, can also be diuretics, or inflict even more excessive fluid loss by causing diarrhea or vomiting. That is one of the reasons why they are generally to be used with caution when conditions like diabetes and cardiovascular disease (among others) are present. Dehydration, especially when combined with insufficient fluid intake, can lead to one of the three major acute complications of diabetes II, non-ketogenic hyperosmolar syndrome, with mortality rate of over 50%.

Of course, there are other adverse side effects - and complications - possible with anti-hypertension drugs, especially at higher than standard doses, and combined with other strong medications used in the study.

And what about cholesterol-lowering drugs? While studies indicate that statins have beneficial effect in reducing risk of adverse cardiovascular events for those with existing cardiovascular disease - which applies to the ACCORD study participants - the effect of combining it with fibrates, or interactions with other drugs used in the study are not well known.

What is known, is that statins and fibrates combined cause dramatically higher incidence of rhabdomyolysis, potentially deadly breakdown of muscle tissue: from approximately 1 in 20,000 with statins alone,

to 1 in 500 for statins combined with fibrates in older patients
with diabetes

(Graham et al.). Since this is the incidence for a year-long period, assuming that roughly half of ~2700 participants in the intense cholesterol arm fit into the "older patient with diabetes" category, a rough statistical estimate for the ACCORD study, with the average
4-year treatment duration, would come to some two dozen cases of rhabdomyolysis resulting from the use of statins/fibrates combo.

It is also suspected for a while that statins and fibrates promote cancer growth. This has been disclosed since early 1990's in their product information sheet. The manufacturer states that they are carcinogenic in animals at concentrations not far from those in humans under standard treatment - especially gemfibrozil, fibrate-type cholesterol lowering medication sold as Lopid, which is carcinogenic in rodents at only 1.3 the human patient concentration.

Note that only about half of deaths during the ACCORD study were due to cardiovascular disease; the rest were caused by other conditions, including cancer.

Continues: ACCORD diabetes II study: Conclusion

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