專題討論8:常見疾病治療新進展工作坊

S8-3
高血壓藥物治療進展
江晨恩
台北榮總心臟內科 陽明大學醫學院

 Hypertension is one of the most important risk factors for atherosclerosis-related mortality and morbidity. In Taiwan, compared with the national 1993 survey, a significant improvement of hypertension awareness, treatment, and control in the 2002 survey was observed. The nation-wide prevalence rates of hypertension, defined by systolic blood pressure more than 140 mmHg or diastolic blood pressure more than 90 mmHg, were 25% in men and 18% in women, and the rate was up to 47% among individuals of age >= 60 years in the 2002 survey. There is a need to have a HT Guideline in Taiwan for better prevention, detection, evaluation, and treatment of HT. The new HT Guideline is highlighted by the following.
The definition of HT was still based on office BP. For high risk patients, such as patients with diabetes, chronic kidney disease, established coronary heart disease (CHD), and CHD equivalents (carotid artery disease, peripheral arterial disease, and abdominal aneurysm), a BP d 130/80mmHg instead of 140/90 mmHg is regarded as high.
Home BP monitoring has better correlations with target organ damage and future CV events. It can also improve patient’s adherence to treatment regimens. This guideline highly recommends home BP monitoring before and during treatment. White-coat HT and masked HT can be detected without difficulty by the use of home BP monitoring.
Life style modification should be undertaken in all patients with high normal blood pressure, prehypertension, patients with definite hypertension, and those required drug treatments. The purpose is to lower blood pressure, to control other risk factors, and to reduce numbers or doses of anti-hypertensive drugs. The lifestyle measures that are widely recommended to lower blood pressure and cardiovascular risks are smoking cessation, weight reduction in the overweight, moderation of alcohol consumption, physical activity, adoption of diet, and reduction of salt consumption.
When a patient needs drug treatment, physicians should “PROCEED” to decide the optimal agent for the patient: First, Previous unfavorable experience of the individual patient to a given class of antihypertensive drug should be carefully sought out because adverse events are the most important cause of non-adherence. Second, Risk factors for an individual patient should be considered. Third, Organ damage, even sub-clinical, or previous associated cardiovascular conditions may favor certain classes of drugs or certain combinations. Fourth, Contraindications or unfavorable conditions should be examined. Fifth, Expense or cost may be taken in account. Sixth, Expert’s or doctor’s judgment is of paramount importance in managing patients. Any guideline can only served as reference in treating individual patient. Finally, Delivery and compliance issue is the key to successful treatment of HT. Physicians should motivate patients and have good communication with individual patient. Simplified treatment with long-acting drugs or by using single-pill combination formula may be required to obtain higher adherence rate.
The main benefits of antihypertensive agents are derived from lowering of BP per se, and are generally independent of the drugs used. Although there are some clinical trials supporting the superiority of one drug or combination over another or other combinations in reducing stroke, end-stage renal disease, or CV events, controlling BP to goal is more important than choosing drug class. There are 5 major classes of drugs for hypertension treatment: thiazide diuretic, beta-blocker (BB), calcium channel blocker (CCB), angiotensin converting enzyme inhibitor (ACEI), and angiotensin receptor blocker (ARB). With the exception of beta-blocker, all these agents are suitable for the initiation and maintenance of antihypertensive treatment either as monotherapy or in combinations. Beta-blockers are only indicated for patients with heart failure, history of ischemic heart disease or myocardial infarction, or hyper-adrenergic state. There are some conditions for which preferred drugs might be considered. Nevertheless, in more than 70% of patients single agent would not be enough, so it seems futile to emphasize the identification of the first preferred drug.
Combination of different drugs is frequently needed in patients with stage 2 HT or in high risk patients when lower targets are pursued. The 2 or 3 different drugs with independent mechanisms could be used in low or standard doses to achieve more BP lowering than up-titration of the monotherapy alone, obviating the frustration of searching for effective monotherapy. A decrease of 20/10 mmHg in SBP/DBP could be expected with a 2-drug combination. In general, the amount of BP decrease by a 2-drug combination is at least the sum of the decrease by individual drug if their mechanisms are independent, with the exception in the combination of ACEI and ARB. Combining drugs from different classes is approximately 5 times more effective in lowering blood pressure than increasing the dose of 1 drug. Furthermore, the goal BP could be achieved more promptly by starting with combination therapy. Similarly, the combination of different drugs in low or standard doses is more likely to be free of side effects compared to higher doses of monotherapy. The combination therapy may have a favorable tolerance profile since the complementary mechanisms of action of the components minimizing their individual side effects. This guideline strongly recommends early combination therapy.
When combination therapy was considered, the A+(C or D) formula is a reasonable first-step combination. Beta-blocker can be used in special conditions as mentioned above, or be combined with a CCB in patients with CHD. If patient’s BP is d 180/110 mmHg, three drug combination of A+C+D may be needed. Combination of a beta-blocker and a thiazide diuretic should be used with great caution since both have diabetogenic potential. Combination of ACEI and ARB is also undesirable according to the result from the ONTARGET study.
Combinations of two drugs in a single tablet (fixed-dose combination, or single-pill combination) are now widely available. Although the fixed dose of the individual components limit the flexibility of upward and downward titration, fixed-dose combinations reduce the tablet number and potentially improve compliance. It has been shown that the non-compliance rate for patients taking the fixed-dose combination is 26% lower compared with free-drug component regimen. They can be used for first-line therapy, provided that initial use of two drugs rather than monotherapy is indicated, and for more rapid achievement of BP goal. Furthermore, it is cheaper than the total cost of individual component and would be widely used in the future.
Treatment of HT in special conditions, such as diabetes, cerebral vascular disease, chronic kidney disease, women, pregnancy, HT emergency, resistant HT, etc., will also be presented.