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Posts Tagged ‘allhat’

idh

  • Hypertension  is  major determinant of cardiovascular health  of our global population
  • Millions suffer,   hundreds of societies ,  and as many guidelines , and drugs are still struggling  to control the menace.
  • An important sub group of HT , (ie IDH ) population has been neglected and never received the scientific interest , which it deserves !
  • In our study it occured in 7.2% of all HT  patients.
  • JNC,  the world authority on HT never considered  IDH as a separate entity, and as of now there is no specific guidelines.
  • And the irony is complete . There is not  a  major study available to analyse the differential effects of anti hypertensive drugs on systolic and diastolic blood pressure.

If  a patient with the BP of 120/96 asks you , “Doctor , will the drug,   you have prescribed , selectively lower my diastolic blood pressure ” what will be your answer ?

A clear ,  I don”t know !

The following paper was presented in the World congress of cardiology Sydney  2002

Isolated  Diastolic Hypertension

S.Venkatesan,S.D.Jayaraj.Gnanavelu, Madras Medical College. Madras, India.

Abstract : Systemic  hypertension  continues to  be a major determinant of cardiovascular  morbidity. While isolated systolic hypertension(ISH) has been identified as a specific clinical entity, isolated  diastolic  hypertension(IDH) has not been reported as a separate group. When we analysed our data from our hypertension   clinic  we found  a distinct subgroup of patients who had  elevated  diastolic blood pressure   with  normal systolic pressure. We report the clinical profile of these patients. 440 newly registered hypertensive  patients between the year 1998-99  formed the study population. All  patients with secondary hypertension  were excluded.. IDH  was defined as  diastolic BP more than 90mmhg and systolic BP less than 140mmhg.

IDH was present in 32(7.2%) patients.  The male female ratio was 3:1, mean age was 42(Range32-56) The mean diastolic pressure was 96 mm (Range 90-110).The mean systolic pressure was 136mm(Range 128-140). LVH was observed in 4 patients(12.5%). Diastolic dysfunction was detected by echocardiography   in 20patients.(62%)

We conclude that isolated diastolic hypertension  constitute a  significant subset among  hypertensive  patients and they need further study regarding the pathogenesis, clinical  presentation and  therapeutic implication.

Link to PPT  will be available soon .

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Let us not forget the basics !

  • HT management has been made  easier with the availability of  many  good drugs , at the same time it has become a complex  issue with as many classification and guidelines.
  • The management of HT has evolved over the decades. Now we have realised  HT  is not a simple number game . Reducing the blood pressure to target levels is not  sufficient and is not the primary aim !.
  • In fact we now know controlling the numbers alone is never going to work  , combined risk factor reduction is of paramount importance.
  • HT per se is less lethal but when it combines with hyperlipidemia and diabetes or smoking  it becomes  aggressive.The blood lipids  especially the LDL molecule  enjoy the high pressure environment  ,   penetrate and invade the vascular endothelium.
  • ASCOT  LLA  study has taught us,   for blood pressure reduction to  be effective and reduce CAD  events one has to reduce thier  lipid levels also.So , for every patient with HT there is not only a target BP but also a target LDL level .

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Final message

The tip for better vascular  health is  , all  hypertensive patients should keep their lipids to optimal levels and all hyperlipidemia patients should keep their BP as low as possible .

“Keep your LDL  as low as  your diastolic blood pressure  and  let us  keep it around 70 -80

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                                                 It is now mandatory for all  journals  to declare the  conflict  of interest by the authors  who are involved in medical research .The purpose apparently is to make all transactions or links  between the researchers and their funding agencies transparent .Even major journals  do not go beyond this . Some ensure it , to appear in the first page of  the article.

 What does the the journals tend to  convey to the reader by publishing the conflicts of interest ?

  •  Does it  mean the article in question  may have a bias or indeed have a bias  ?  and readers are warned  hereby !
  •  Do they send across a message  that the  article may not be really a genuine one and the judgement is left to the the consumers of the articles ?

How often a journal article is rejected purely on the basis of  conflicts of interest ?

Most of  journal articles are rejected  for poor methodology, statistical analysis and so forth .We don’t know how often a paper is rejected  due to a conflict issue per se.If this could happen ,bulk  of drug trials would face a torrid time from the editors.

Why , even the leading scientific  journals never indulge in grading the significance of the conflict ?

Here is an example .

accomplish

nejm1

The much hyped drug trial on Hypertension “ACCOMPLISH”  was published in the  world’s most prestigious medical journal recently .It  left  it to the readers to  have their  own assessment  on the conflict issue.

  The consequence of not , grading and investigating  about the conflicts could have  serious  global health  implications both financially and academically .

This study was designed, formulated, completed and published  with a single hidden aim of neutralising the land mark trial  of ALLHAT which recommended diuretics as a first line drug in HT.Apparently diuretics are very  cheap  , effective  generic drugs.

 Is it a scientific rule  that  the  latest evidence  ,  should always prevail over the older evidence ?

No. Science can never have such a rule ! The question is how good and genuine is the evidence.
Just because an evidence is current , it does not  attain a scientific sanctity !

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Is it true , once a patient is labelled as a hypertensive he remains  hypertensive life long ? Is it possible to withdraw antihypertensive drugs  permanently ?

  • Systemic  hypertension is the most common clinical entity and it forms the bulk of the physician consultations world over.
  • The anti hypertensive drugs are  one of the most commonly  prescribed medication  by the medical professionals .
  •  It is estimated , the major chunk of  revenue to pharma industry is contributed by antihypertensive  drugs.
  •  SHT , is being maintained  as a  major , global cardiovascular risk factor , by  periodically refixing the target blood pressure  to lower levels  by various committees.
  • The terminology of pre hypertension for blood pressure between 120-140 was hugely controversial    and some societies refused  to accept this entity.

Is there a case for withdrawal of anti hypertensive agents  among our patients ?

Yes , in fact there is a strong case for it.

While on the one hand there is a sustained effort ( By whom !)  to increase the drug usage , very early in the course of hypertension , there is also a silent progress in our knowledge ,  regarding withdrawl of anti hypertensive agents in all those undeserving patients .

It is estimated 42% *of the so called hypertensives especially elderly can be successfully weaned of anti hypertensive drugs with out any adverse effect.( Mark R Nelson BMJ. 2002 October 12; 325(7368): 815.)

What are the situations where we can successfully with draw anti hypertensive drugs?

  • The most common group of patients  are the ones, where  the anti hypertensive drugs are  started prematurely , with out giving an option for non drug life style  approach.These patients and their physicians continue to believe , anti HT drugs are sacred and essential !
  • There is another  major group of patients who have had a temporary  elevation of BP due to a stressful environment.These patients  get drugs permanently for a temporary problem . These patients need  to be reassessed.
  • Some of the elderly  patients,  with the onset of  age  related autonomic dysfunction ,these  drugs are poorly tolerated and  even have  disastrous effects .In this population  it is desirable , to wean off the anti HT drugs  and switched over to life style  medication whenever possible.

Final message

Essential or primary hypertension is not a permanent  disease, in bulk of our population. It reflects the  state of  the  blood pressure on a day to day basis  and is a continuous variable. All patients who have been labelled as hypertensives( Either by us or others) should be constantly reviewed  and considered for withdrawal of the drugs if possible.

* Note this rule does not apply in all secondary hypertensions, during  emergencies, uncontrolled hyper tension with co existing CAD /diabetes /dyslipidemias etc .

Please refer to these forgotten Landmark articles

Does Withdrawl of Anti hypertensive Medication 

Increase the Risk of Cardiovascular Events?

The TONE study

Source: The American Journal of Cardiology, Volume 82, Number 12, 15 December 1998 , pp. 1501-1508(8)

http://www.ncbi.nlm.nih.gov/pubmed/9874055

Conclusion of TONE study

The study shows that antihypertensive medication can be safely withdrawn in older persons without clinical evidence of cardiovascular disease who do not have diastolic pressure > or = 150/90 mm Hg at withdrawal, providing that good BP control can be maintained with nonpharmacologic therapy

 

Some of the references for successful withdrawl of antihypertenive drugs

1.Nelson, M; Reid, C; Krum, H; McNeil, J. A systematic review of predictors of maintenance of normotension after withdrawal of antihypertensive drugs. Am J Hypertens. 2001;14:98–105. [PubMed]
2.
Wing, LMH; Reid, CM; Ryan, P; Beilin, LJ; Brown, MA; Jennings, GLR, et al. Second Australian nationalbloodpressure study (ANBP2): Australian comparative outcome trial of ACE inhibitor- and diuretic-based treatment of hypertension in the elderly. Clin Exp Pharmacol Physiol. 1997;19:779–791.
3.
Lee, J. Odds ratio or relative risk for cross-sectional data. Int J Epidemiol. 1994;723:201–203. [PubMed]
4.
Lin, D; Wei, L. The robust inference for the Cox proportional hazards model. J Am Stat Assoc. 1989;84:1074–1079.
5.
Veterans Administration Cooperative Study Group on Antihypertensive Drugs. Return of elevated blood pressure after withdrawal of antihypertensive drugs. Circulation. 1975;51:1107–1113. [PubMed]
6.
Medical Research Council Working Party on the Management of Hypertension. Course of blood pressure in mild hypertensives after withdrawal of long term antihypertensive treatment. BMJ. 1986;293:988–992. [PubMed]
7.
Alderman, MH; Davis, TK; Gerber, LM; Robb, M. Antihypertensive drug therapy withdrawalin a general population. Arch Intern Med. 1986;146:1309–1311. [PubMed]
8.
Blaufox, MD; Langford, HG; Oberman, A; Hawkins, CM; Wassertheil-Smoller, S; Cutter, GR. Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH). J Hypertension. 1984;2(suppl 3):179–181.
9.
Mitchell, A; Haynes, RB; Adsett, CA; Bellissimo, A; Wilczynski, N. The likelihood of remaining normotensive following antihypertensive drug withdrawal. J Gen Intern Med. 1989;4:221–225. [PubMed]
10.
Myers, MG; Reeves, RA; Oh, PI; Joyner, CD. Overtreatment of hypertension in the community? Am J Hypertens. 1996;9:419–425. [PubMed]
11.
Stamler, R; Stamler, J; Grimm, R; Gosch, F; Dyer, R; Berman, R, et al. Trial of control of hypertension by nutritional means: three year results. J Hypertens. 1984;2(suppl 3):167–170.
12.
Takata, Y; Yoshizumi, T; Ito, Y; Ueno, M; Tsukashima, A; Iwase, M, et al. Comparison of withdrawing antihypertensivetherapy between diuretics and angiotensinconverting enzyme inhibitors in essential hypertensives. Am Heart J. 1992;124:1574–1580. [PubMed]
13.
Whelton, PK; Appel, LJ; Espeland, MA; Applegate, WB; Ettinger, WH; Kostis, JB, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomised controlled trial of nonpharmacological interventions in the elderly (TONE). JAMA. 1998;279:839–846. [PubMed]
14.
Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on death from cardiovascular causes, myocardial infarction, and stroke in high-risk patients. N Engl J Med. 2000;342:145–153. [PubMed]
15.
Howes, L; Krum, H. Withdrawing antihypertensive treatment. Curr Therapeutics. 1988;November:15–20.
16.
Fotherby, MD; Harper, GD; Potter, JF. General practitioners’ management of hypertension in elderly patients. BMJ. 1992;305:750–752. [PubMed]
17.
Jennings, GL; Reid, CM; Sudhir, K; Laufer, E; Korner, PI. Factors influencing the success of withdrawal of antihypertensive drug therapy. Blood Press Suppl. 1995;2:99–107. [PubMed]

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Diuretics are the most commonly prescribed anti hypertensive agents.Thiazide diuretics which  was introduced many decades ago ,  lost popularity  in recent years ,  again got a second life after  the publication of ALLHAT trial recently. Now diuretics has become the  the drug of first choice in almost any hypertension unless any specific contraindication.

The most commonly used thaizide is hydrochlorthiazide ,and chlorthalidone.The blood pressure reducing effect is so consistent and smooth , all the currently popular molecules like ACE inhibitors and ARBs come with a combination with thiazide. While every one is clear diuretics are  effective anti hypertensive agent How it does is not clear.

How does a diuretic reduce blood pressure?

A. The exact mechanism is not clear. May not be uniformly effective in all patients  with HT.

B . Salt sensitive HT respond well to diuretics.

C. Volume correction /free water clearance might be a factor

D. Direct effect on vascular smoth muscle documented.The sodium transporter is blocked and  hence   calcium : sodium exchange is prevented .This depletes  intracellular calcium  in vascular smooth muscle cells .Less calcium for actin myosin interaction and hence vasodilatation

E. Thiazides combine well with all other antihypertensive drugs (ACEI, ARB, Beata blockers, calcium blockers)

F. Loop diuretics  like frusemide  can never be  a good antihypertensive agent.

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